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Gene Information
Gene symbol: GAD2
Gene name: glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa)
HGNC ID: 4093
Synonyms: GAD65
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1370298 | Insulin-dependent diabetes mellitus (IDDM) is thought to result from the autoimmune destruction of the insulin-producing beta cells of the pancreas. |
| 2 | 1370298 | Years before IDDM symptoms appear, we can detect autoantibodies to one or both forms of glutamate decarboxylase (GAD65 and GAD67), synthesized from their respective cDNAs in a bacterial expression system. |
| 3 | 1370298 | Although the level of GAD autoantibodies generally decline after IDDM onset, patients with IDDM-associated neuropathies have high levels of antibodies to GAD, years after the appearance of clinical IDDM. |
| 4 | 1370298 | We note a striking sequence similarity between the two GADs and Coxsackievirus, a virus that has been associated with IDDM both in humans and in experimental animals. |
| 5 | 1549570 | We report the isolation and sequencing of cDNAs encoding two human glutamate decarboxylases (GADs; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), GAD65 and GAD67. |
| 6 | 1549570 | In situ hybridization of fluorescently labeled GAD probes to human chromosomes localizes the human GAD65 gene to chromosome 10p11.23 and the human GAD67 gene to chromosome 2q31. |
| 7 | 1549570 | We report the isolation and sequencing of cDNAs encoding two human glutamate decarboxylases (GADs; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), GAD65 and GAD67. |
| 8 | 1549570 | In situ hybridization of fluorescently labeled GAD probes to human chromosomes localizes the human GAD65 gene to chromosome 10p11.23 and the human GAD67 gene to chromosome 2q31. |
| 9 | 1924293 | GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. |
| 10 | 1924293 | Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. |
| 11 | 1924293 | Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. |
| 12 | 1924293 | GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. |
| 13 | 1924293 | The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. |
| 14 | 1924293 | The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined. |
| 15 | 1924293 | GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. |
| 16 | 1924293 | Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. |
| 17 | 1924293 | Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. |
| 18 | 1924293 | GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. |
| 19 | 1924293 | The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. |
| 20 | 1924293 | The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined. |
| 21 | 1924293 | GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. |
| 22 | 1924293 | Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. |
| 23 | 1924293 | Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. |
| 24 | 1924293 | GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. |
| 25 | 1924293 | The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. |
| 26 | 1924293 | The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined. |
| 27 | 1924293 | GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. |
| 28 | 1924293 | Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. |
| 29 | 1924293 | Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. |
| 30 | 1924293 | GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. |
| 31 | 1924293 | The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. |
| 32 | 1924293 | The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined. |
| 33 | 1939164 | The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic acid decarboxylase. |
| 34 | 1939164 | Comparative analysis of the brain and beta-cell forms of GAD show that GAD65 and GAD64 in pancreatic beta-cells correspond to the larger and smaller forms of GAD in brain, respectively. |
| 35 | 7505244 | GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes. |
| 36 | 7505244 | Glutamic acid decarboxylase (GAD) is a major islet cell autoantigen in insulin-dependent diabetes mellitus (IDDM), and autoantibodies are found in high frequencies in patients with recent-onset IDDM, stiff-man syndrome (SMS), and autoimmune polyendocrine syndrome type I (APS I). |
| 37 | 7505244 | In this study, we examined the reactivity of anti-GAD-containing sera from 7 patients with IDDM, 4 patients with SMS, and 5 patients with APS I. |
| 38 | 7505244 | All sera immunoprecipitated GAD from [35S]methionine-labeled rat islet lysates and the sera from patients with SMS and APS I, but none of the IDDM patients' sera, identified the GAD protein in Western blots. |
| 39 | 7505244 | Two of four SMS patients' sera and 5 of 5 APS I patients' sera, in contrast to 0 of 7 IDDM patients' sera, inhibited the enzymatic activity of GAD. |
| 40 | 7505244 | When the various sera were tested with the GAD65 and GAD67 isoforms, produced separately by transient expression in COS cells, the enzymatic activity of GAD65 was inhibited by sera from patients with SMS and APS I, whereas no effect on the GAD67 activity was observed. |
| 41 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 42 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 43 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 44 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 45 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 46 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 47 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 48 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 49 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 50 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 51 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 52 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 53 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 54 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 55 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 56 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 57 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 58 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 59 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 60 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 61 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 62 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 63 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 64 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 65 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 66 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 67 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 68 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 69 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 70 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 71 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 72 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 73 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 74 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 75 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 76 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 77 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 78 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 79 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 80 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 81 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 82 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 83 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 84 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 85 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 86 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 87 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 88 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 89 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 90 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 91 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 92 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 93 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 94 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 95 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 96 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 97 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 98 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 99 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 100 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 101 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 102 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 103 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 104 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 105 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 106 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 107 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 108 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 109 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 110 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 111 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 112 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 113 | 7519242 | Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. |
| 114 | 7519242 | Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. |
| 115 | 7519242 | Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. |
| 116 | 7519242 | All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. |
| 117 | 7519242 | Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. |
| 118 | 7519242 | The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. |
| 119 | 7519242 | The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. |
| 120 | 7519242 | The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. |
| 121 | 7519242 | The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses. |
| 122 | 7523207 | The possible role of amino acid sequence and epitope homologies between a protein P2-C of Coxsackie virus B4 and human GAD in the development of host-specific immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry) was investigated. |
| 123 | 7523207 | Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection. |
| 124 | 7523207 | All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced. |
| 125 | 7523207 | P2-C antiserum immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67 antisera both immunocomplexed with the two GADs from these sources. |
| 126 | 7523207 | A number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65 peptides, whereas only a few reacted with GAD67 peptide. |
| 127 | 7523207 | The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD. |
| 128 | 7523207 | The possible role of amino acid sequence and epitope homologies between a protein P2-C of Coxsackie virus B4 and human GAD in the development of host-specific immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry) was investigated. |
| 129 | 7523207 | Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection. |
| 130 | 7523207 | All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced. |
| 131 | 7523207 | P2-C antiserum immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67 antisera both immunocomplexed with the two GADs from these sources. |
| 132 | 7523207 | A number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65 peptides, whereas only a few reacted with GAD67 peptide. |
| 133 | 7523207 | The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD. |
| 134 | 7523207 | The possible role of amino acid sequence and epitope homologies between a protein P2-C of Coxsackie virus B4 and human GAD in the development of host-specific immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry) was investigated. |
| 135 | 7523207 | Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection. |
| 136 | 7523207 | All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced. |
| 137 | 7523207 | P2-C antiserum immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67 antisera both immunocomplexed with the two GADs from these sources. |
| 138 | 7523207 | A number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65 peptides, whereas only a few reacted with GAD67 peptide. |
| 139 | 7523207 | The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD. |
| 140 | 7523207 | The possible role of amino acid sequence and epitope homologies between a protein P2-C of Coxsackie virus B4 and human GAD in the development of host-specific immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry) was investigated. |
| 141 | 7523207 | Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection. |
| 142 | 7523207 | All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced. |
| 143 | 7523207 | P2-C antiserum immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67 antisera both immunocomplexed with the two GADs from these sources. |
| 144 | 7523207 | A number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65 peptides, whereas only a few reacted with GAD67 peptide. |
| 145 | 7523207 | The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD. |
| 146 | 7523207 | The possible role of amino acid sequence and epitope homologies between a protein P2-C of Coxsackie virus B4 and human GAD in the development of host-specific immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry) was investigated. |
| 147 | 7523207 | Peptide antibodies to the P2-C protein, GAD65, and GAD67 were raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and immunoblotting with GAD purified from the brain and pancreas of mice that develop hyperglycemia after the infection. |
| 148 | 7523207 | All three peptide antisera reacted very strongly with homologous peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65 antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67 although cross-reaction between the two GADs was quite pronounced. |
| 149 | 7523207 | P2-C antiserum immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67 antisera both immunocomplexed with the two GADs from these sources. |
| 150 | 7523207 | A number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65 peptides, whereas only a few reacted with GAD67 peptide. |
| 151 | 7523207 | The immunoreactivity of the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption with mouse GAD. |
| 152 | 7525393 | The 65-kDa isoform of glutamic acid decarboxylase (GAD65) has been implicated in autoimmune diabetes in NOD mice, but the role of the 67-kDa GAD isoform (GAD67) is less clear. |
| 153 | 7532143 | Although most individuals with insulin-dependent diabetes mellitus (IDDM) have autoantibodies to glutamic acid decarboxylase (GAD), antibodies to GAD are also present in some individuals with a low risk of developing diabetes. |
| 154 | 7532143 | The GAD autoantibodies of IDDM are specific for the GAD65 isoform, do not bind denatured GAD protein, and target epitope(s) dependent on conformation of the protein. |
| 155 | 7532143 | However, the IDDM epitopes have been difficult to further define because the antibodies do not bind GAD protein fragments or synthetic peptides. |
| 156 | 7532143 | Since the GAD67 isoform is highly homologous to GAD65 but is usually not a target of the GAD autoantibodies in IDDM sera, we created six GAD65/GAD67 chimeric proteins to maintain the overall GAD protein conformation and used these chimeric proteins to map conformation-dependent epitopes of GAD65 targeted by IDDM sera. |
| 157 | 7532143 | We find that the GAD binding present in most IDDM sera (n = 11 of 12) is composed of two distinct GAD antibody specificities that target different conformation-dependent regions of the GAD65 protein, one that is located between amino acids 240 and 435 (termed IDDM-E1) and one that is located between amino acids 451 and 570 (termed IDDM-E2). |
| 158 | 7532143 | Identification of epitopes targeted by IDDM sera may allow one to distinguish between GAD antibody-positive individuals at high and low risk of developing IDDM and to determine if differences in the autoimmune repertoire directed at GAD are present. |
| 159 | 7532143 | The chimeric GAD65/GAD67 proteins may also be useful in designing GAD assays specific for IDDM. |
| 160 | 7532143 | Although most individuals with insulin-dependent diabetes mellitus (IDDM) have autoantibodies to glutamic acid decarboxylase (GAD), antibodies to GAD are also present in some individuals with a low risk of developing diabetes. |
| 161 | 7532143 | The GAD autoantibodies of IDDM are specific for the GAD65 isoform, do not bind denatured GAD protein, and target epitope(s) dependent on conformation of the protein. |
| 162 | 7532143 | However, the IDDM epitopes have been difficult to further define because the antibodies do not bind GAD protein fragments or synthetic peptides. |
| 163 | 7532143 | Since the GAD67 isoform is highly homologous to GAD65 but is usually not a target of the GAD autoantibodies in IDDM sera, we created six GAD65/GAD67 chimeric proteins to maintain the overall GAD protein conformation and used these chimeric proteins to map conformation-dependent epitopes of GAD65 targeted by IDDM sera. |
| 164 | 7532143 | We find that the GAD binding present in most IDDM sera (n = 11 of 12) is composed of two distinct GAD antibody specificities that target different conformation-dependent regions of the GAD65 protein, one that is located between amino acids 240 and 435 (termed IDDM-E1) and one that is located between amino acids 451 and 570 (termed IDDM-E2). |
| 165 | 7532143 | Identification of epitopes targeted by IDDM sera may allow one to distinguish between GAD antibody-positive individuals at high and low risk of developing IDDM and to determine if differences in the autoimmune repertoire directed at GAD are present. |
| 166 | 7532143 | The chimeric GAD65/GAD67 proteins may also be useful in designing GAD assays specific for IDDM. |
| 167 | 7532143 | Although most individuals with insulin-dependent diabetes mellitus (IDDM) have autoantibodies to glutamic acid decarboxylase (GAD), antibodies to GAD are also present in some individuals with a low risk of developing diabetes. |
| 168 | 7532143 | The GAD autoantibodies of IDDM are specific for the GAD65 isoform, do not bind denatured GAD protein, and target epitope(s) dependent on conformation of the protein. |
| 169 | 7532143 | However, the IDDM epitopes have been difficult to further define because the antibodies do not bind GAD protein fragments or synthetic peptides. |
| 170 | 7532143 | Since the GAD67 isoform is highly homologous to GAD65 but is usually not a target of the GAD autoantibodies in IDDM sera, we created six GAD65/GAD67 chimeric proteins to maintain the overall GAD protein conformation and used these chimeric proteins to map conformation-dependent epitopes of GAD65 targeted by IDDM sera. |
| 171 | 7532143 | We find that the GAD binding present in most IDDM sera (n = 11 of 12) is composed of two distinct GAD antibody specificities that target different conformation-dependent regions of the GAD65 protein, one that is located between amino acids 240 and 435 (termed IDDM-E1) and one that is located between amino acids 451 and 570 (termed IDDM-E2). |
| 172 | 7532143 | Identification of epitopes targeted by IDDM sera may allow one to distinguish between GAD antibody-positive individuals at high and low risk of developing IDDM and to determine if differences in the autoimmune repertoire directed at GAD are present. |
| 173 | 7532143 | The chimeric GAD65/GAD67 proteins may also be useful in designing GAD assays specific for IDDM. |
| 174 | 7532143 | Although most individuals with insulin-dependent diabetes mellitus (IDDM) have autoantibodies to glutamic acid decarboxylase (GAD), antibodies to GAD are also present in some individuals with a low risk of developing diabetes. |
| 175 | 7532143 | The GAD autoantibodies of IDDM are specific for the GAD65 isoform, do not bind denatured GAD protein, and target epitope(s) dependent on conformation of the protein. |
| 176 | 7532143 | However, the IDDM epitopes have been difficult to further define because the antibodies do not bind GAD protein fragments or synthetic peptides. |
| 177 | 7532143 | Since the GAD67 isoform is highly homologous to GAD65 but is usually not a target of the GAD autoantibodies in IDDM sera, we created six GAD65/GAD67 chimeric proteins to maintain the overall GAD protein conformation and used these chimeric proteins to map conformation-dependent epitopes of GAD65 targeted by IDDM sera. |
| 178 | 7532143 | We find that the GAD binding present in most IDDM sera (n = 11 of 12) is composed of two distinct GAD antibody specificities that target different conformation-dependent regions of the GAD65 protein, one that is located between amino acids 240 and 435 (termed IDDM-E1) and one that is located between amino acids 451 and 570 (termed IDDM-E2). |
| 179 | 7532143 | Identification of epitopes targeted by IDDM sera may allow one to distinguish between GAD antibody-positive individuals at high and low risk of developing IDDM and to determine if differences in the autoimmune repertoire directed at GAD are present. |
| 180 | 7532143 | The chimeric GAD65/GAD67 proteins may also be useful in designing GAD assays specific for IDDM. |
| 181 | 7532577 | Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67. |
| 182 | 7532577 | GAD65 is preferentially expressed in human islets and recognized by autoantibodies in IDD, but which form primarily elicits GAD autoimmunity is unknown. |
| 183 | 7532577 | In ribonuclease protection assays, both forms of GAD messenger RNA (mRNA) were detected in human islets, although GAD65 mRNA was 200 times more abundant than GAD67 mRNA. |
| 184 | 7532577 | Immunoblotting of islets with GAD form-specific antisera revealed GAD65, but not GAD67. |
| 185 | 7532577 | Although GAD67 may share cross-reactive epitopes with GAD65, these findings do not exclude the possibility that autoimmunity to GAD arises as a consequence of the aberrant up-regulation of GAD67 in human islets. |
| 186 | 7532577 | Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67. |
| 187 | 7532577 | GAD65 is preferentially expressed in human islets and recognized by autoantibodies in IDD, but which form primarily elicits GAD autoimmunity is unknown. |
| 188 | 7532577 | In ribonuclease protection assays, both forms of GAD messenger RNA (mRNA) were detected in human islets, although GAD65 mRNA was 200 times more abundant than GAD67 mRNA. |
| 189 | 7532577 | Immunoblotting of islets with GAD form-specific antisera revealed GAD65, but not GAD67. |
| 190 | 7532577 | Although GAD67 may share cross-reactive epitopes with GAD65, these findings do not exclude the possibility that autoimmunity to GAD arises as a consequence of the aberrant up-regulation of GAD67 in human islets. |
| 191 | 7532577 | Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67. |
| 192 | 7532577 | GAD65 is preferentially expressed in human islets and recognized by autoantibodies in IDD, but which form primarily elicits GAD autoimmunity is unknown. |
| 193 | 7532577 | In ribonuclease protection assays, both forms of GAD messenger RNA (mRNA) were detected in human islets, although GAD65 mRNA was 200 times more abundant than GAD67 mRNA. |
| 194 | 7532577 | Immunoblotting of islets with GAD form-specific antisera revealed GAD65, but not GAD67. |
| 195 | 7532577 | Although GAD67 may share cross-reactive epitopes with GAD65, these findings do not exclude the possibility that autoimmunity to GAD arises as a consequence of the aberrant up-regulation of GAD67 in human islets. |
| 196 | 7532577 | Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67. |
| 197 | 7532577 | GAD65 is preferentially expressed in human islets and recognized by autoantibodies in IDD, but which form primarily elicits GAD autoimmunity is unknown. |
| 198 | 7532577 | In ribonuclease protection assays, both forms of GAD messenger RNA (mRNA) were detected in human islets, although GAD65 mRNA was 200 times more abundant than GAD67 mRNA. |
| 199 | 7532577 | Immunoblotting of islets with GAD form-specific antisera revealed GAD65, but not GAD67. |
| 200 | 7532577 | Although GAD67 may share cross-reactive epitopes with GAD65, these findings do not exclude the possibility that autoimmunity to GAD arises as a consequence of the aberrant up-regulation of GAD67 in human islets. |
| 201 | 7532577 | Glutamic acid decarboxylase (GAD), a target of both autoantibodies and autoreactive T-cells in insulin-dependent diabetes (IDD), exists as two homologous forms, GAD65 and GAD67. |
| 202 | 7532577 | GAD65 is preferentially expressed in human islets and recognized by autoantibodies in IDD, but which form primarily elicits GAD autoimmunity is unknown. |
| 203 | 7532577 | In ribonuclease protection assays, both forms of GAD messenger RNA (mRNA) were detected in human islets, although GAD65 mRNA was 200 times more abundant than GAD67 mRNA. |
| 204 | 7532577 | Immunoblotting of islets with GAD form-specific antisera revealed GAD65, but not GAD67. |
| 205 | 7532577 | Although GAD67 may share cross-reactive epitopes with GAD65, these findings do not exclude the possibility that autoimmunity to GAD arises as a consequence of the aberrant up-regulation of GAD67 in human islets. |
| 206 | 7556984 | Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). |
| 207 | 7556984 | Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)65, 37,000/40,000 M(r) islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. |
| 208 | 7556984 | Islet cell antibodies were detected in 88% of IDDM patients and 81% with pre-IDDM, GAD65 antibodies in 70% of IDDM patients and 89% with pre-IDDM, and antibodies to 37,000/40,000 M(r) islet tryptic fragments in 54% of IDDM patients and in 48% with pre-IDDM. |
| 209 | 7556984 | All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD65 antibodies had antibodies to 37,000/40,000 M(r) islet tryptic fragments, and all but one had disease onset before age 15 years. |
| 210 | 7556984 | The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD65 antibodies and antibodies to 37,000/40,000 M(r) islet tryptic fragments has the potential to identify more than 90% of future cases of IDDM. |
| 211 | 7556984 | Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). |
| 212 | 7556984 | Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)65, 37,000/40,000 M(r) islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. |
| 213 | 7556984 | Islet cell antibodies were detected in 88% of IDDM patients and 81% with pre-IDDM, GAD65 antibodies in 70% of IDDM patients and 89% with pre-IDDM, and antibodies to 37,000/40,000 M(r) islet tryptic fragments in 54% of IDDM patients and in 48% with pre-IDDM. |
| 214 | 7556984 | All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD65 antibodies had antibodies to 37,000/40,000 M(r) islet tryptic fragments, and all but one had disease onset before age 15 years. |
| 215 | 7556984 | The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD65 antibodies and antibodies to 37,000/40,000 M(r) islet tryptic fragments has the potential to identify more than 90% of future cases of IDDM. |
| 216 | 7556984 | Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). |
| 217 | 7556984 | Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)65, 37,000/40,000 M(r) islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. |
| 218 | 7556984 | Islet cell antibodies were detected in 88% of IDDM patients and 81% with pre-IDDM, GAD65 antibodies in 70% of IDDM patients and 89% with pre-IDDM, and antibodies to 37,000/40,000 M(r) islet tryptic fragments in 54% of IDDM patients and in 48% with pre-IDDM. |
| 219 | 7556984 | All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD65 antibodies had antibodies to 37,000/40,000 M(r) islet tryptic fragments, and all but one had disease onset before age 15 years. |
| 220 | 7556984 | The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD65 antibodies and antibodies to 37,000/40,000 M(r) islet tryptic fragments has the potential to identify more than 90% of future cases of IDDM. |
| 221 | 7561152 | GAD65 autoantibodies occur frequently in insulin-dependent diabetic patients and is a useful marker for IDDM. |
| 222 | 7561152 | In an immunoassay to detect autoantibodies against the proinsulin converting enzyme 2 (PC-2) no such antibodies were detected in IDDM patients. |
| 223 | 7578849 | Association between antibodies to the MR 67,000 isoform of glutamate decarboxylase (GAD) and type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune polyendocrine syndrome type II. |
| 224 | 7578849 | By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. |
| 225 | 7578849 | Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. |
| 226 | 7578849 | Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). |
| 227 | 7578849 | In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). |
| 228 | 7578849 | The levels of GAD65 (142 +/- 90 AU) and GAD67 antibodies (178 +/- 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 +/- 85 AU and 93 +/- 57 AU) (p < 0.02). |
| 229 | 7578849 | No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. |
| 230 | 7578849 | Association between antibodies to the MR 67,000 isoform of glutamate decarboxylase (GAD) and type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune polyendocrine syndrome type II. |
| 231 | 7578849 | By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. |
| 232 | 7578849 | Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. |
| 233 | 7578849 | Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). |
| 234 | 7578849 | In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). |
| 235 | 7578849 | The levels of GAD65 (142 +/- 90 AU) and GAD67 antibodies (178 +/- 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 +/- 85 AU and 93 +/- 57 AU) (p < 0.02). |
| 236 | 7578849 | No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. |
| 237 | 7578849 | Association between antibodies to the MR 67,000 isoform of glutamate decarboxylase (GAD) and type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune polyendocrine syndrome type II. |
| 238 | 7578849 | By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. |
| 239 | 7578849 | Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. |
| 240 | 7578849 | Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). |
| 241 | 7578849 | In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). |
| 242 | 7578849 | The levels of GAD65 (142 +/- 90 AU) and GAD67 antibodies (178 +/- 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 +/- 85 AU and 93 +/- 57 AU) (p < 0.02). |
| 243 | 7578849 | No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. |
| 244 | 7578849 | Association between antibodies to the MR 67,000 isoform of glutamate decarboxylase (GAD) and type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune polyendocrine syndrome type II. |
| 245 | 7578849 | By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. |
| 246 | 7578849 | Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. |
| 247 | 7578849 | Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). |
| 248 | 7578849 | In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). |
| 249 | 7578849 | The levels of GAD65 (142 +/- 90 AU) and GAD67 antibodies (178 +/- 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 +/- 85 AU and 93 +/- 57 AU) (p < 0.02). |
| 250 | 7578849 | No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. |
| 251 | 7589826 | The presence of serum islet cell cytoplasmic antibodies (ICAs) is a standard autoimmune marker for insulin-dependent diabetes mellitus (IDDM). |
| 252 | 7589826 | We tested 129 IDDM sera for antibodies to ICA512 (anti-ICA512), antibodies to GAD (anti-GAD), and ICAs; we tested for inhibition of ICAs with purified recombinant ICA512 and sheep brain GAD; and we tested for immunofluorescence reactivity on COS7 cells transfected with cDNA clones encoding ICA512 and GAD65. |
| 253 | 7589826 | Anti-ICA512 and anti-GAD antibodies were demonstrable by indirect immunofluorescence on transfected COS7 cells, and ICA could be inhibited using either recombinant ICA512 or purified brain GAD. |
| 254 | 7594559 | Identification of protein tyrosine phosphatase-like IA2 (islet cell antigen 512) as the insulin-dependent diabetes-related 37/40K autoantigen and a target of islet-cell antibodies. |
| 255 | 7594559 | The majority of patients with insulin-dependent diabetes (IDDM) have Abs to 40- and/or 37-kDa tryptic fragments (37/40K-Abs) deriving from an unidentified islet cell membrane protein distinct from glutamate decarboxylase (GAD). |
| 256 | 7594559 | Recently, autoantibodies against ICA512, which has identity with the protein tyrosine phosphatase-like protein IA2, were reported. |
| 257 | 7594559 | Combined detection of Abs to IA2 and GAD65 in a single radio-binding assay identified Abs in 88 of 100 IDDM patients, and potentially facilitates population screening for IDDM risk assessment. |
| 258 | 7681990 | All the MICAs specifically recognized the smaller GAD protein, GAD65, and did not recognize the nonallelic GAD67 protein. |
| 259 | 7714099 | Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. |
| 260 | 7714099 | In this context, we have measured the proliferative responses of peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate decarboxylase (GAD65) by means of 3H thymidine incorporation. |
| 261 | 7714099 | We have also studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow cytometric analysis. |
| 262 | 7714099 | PBMC obtained from 47 patients with Graves' disease (GD) [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM), and 20 normal controls (N), were cultured for 7 days in the presence or absence of the pool peptides representing 3 different segments of TSHR or GAD65 at final concentration of 30 micrograms/mL or 10 micrograms/mL. |
| 263 | 7714099 | The proportion of subjects whose PBMC gave a positive proliferative response with a stimulation index (SI) of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N group. |
| 264 | 7714099 | The CD4+ T lymphocytes from hyper GD group were significantly more activated by TSHR peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to their thyroid hormone levels. |
| 265 | 7714099 | Quite differently, the activation of CD8+ T lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was impaired compared to HT, IDDM, and the N group; in contrast to the findings with CD4+ T lymphocytes, this was independent of thyroid hormone levels. |
| 266 | 7714099 | On the other hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was impaired compared to the GD and N groups. |
| 267 | 7714099 | In conclusion, the activation of CD8+ T lymphocytes from GD and IDDM by relevant antigens (i.e. |
| 268 | 7714099 | TSHR peptides for GD and GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. |
| 269 | 7714099 | GAD65 for GD and TSHR peptides for IDDM). |
| 270 | 7714099 | There was also a modest stimulation of CD8+ T cells from all groups by tetanus toxoid and cardiac myosin light chain peptide, both irrelevant antigens. |
| 271 | 7714099 | Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. |
| 272 | 7714099 | In this context, we have measured the proliferative responses of peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate decarboxylase (GAD65) by means of 3H thymidine incorporation. |
| 273 | 7714099 | We have also studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow cytometric analysis. |
| 274 | 7714099 | PBMC obtained from 47 patients with Graves' disease (GD) [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM), and 20 normal controls (N), were cultured for 7 days in the presence or absence of the pool peptides representing 3 different segments of TSHR or GAD65 at final concentration of 30 micrograms/mL or 10 micrograms/mL. |
| 275 | 7714099 | The proportion of subjects whose PBMC gave a positive proliferative response with a stimulation index (SI) of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N group. |
| 276 | 7714099 | The CD4+ T lymphocytes from hyper GD group were significantly more activated by TSHR peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to their thyroid hormone levels. |
| 277 | 7714099 | Quite differently, the activation of CD8+ T lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was impaired compared to HT, IDDM, and the N group; in contrast to the findings with CD4+ T lymphocytes, this was independent of thyroid hormone levels. |
| 278 | 7714099 | On the other hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was impaired compared to the GD and N groups. |
| 279 | 7714099 | In conclusion, the activation of CD8+ T lymphocytes from GD and IDDM by relevant antigens (i.e. |
| 280 | 7714099 | TSHR peptides for GD and GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. |
| 281 | 7714099 | GAD65 for GD and TSHR peptides for IDDM). |
| 282 | 7714099 | There was also a modest stimulation of CD8+ T cells from all groups by tetanus toxoid and cardiac myosin light chain peptide, both irrelevant antigens. |
| 283 | 7714099 | Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. |
| 284 | 7714099 | In this context, we have measured the proliferative responses of peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate decarboxylase (GAD65) by means of 3H thymidine incorporation. |
| 285 | 7714099 | We have also studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow cytometric analysis. |
| 286 | 7714099 | PBMC obtained from 47 patients with Graves' disease (GD) [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM), and 20 normal controls (N), were cultured for 7 days in the presence or absence of the pool peptides representing 3 different segments of TSHR or GAD65 at final concentration of 30 micrograms/mL or 10 micrograms/mL. |
| 287 | 7714099 | The proportion of subjects whose PBMC gave a positive proliferative response with a stimulation index (SI) of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N group. |
| 288 | 7714099 | The CD4+ T lymphocytes from hyper GD group were significantly more activated by TSHR peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to their thyroid hormone levels. |
| 289 | 7714099 | Quite differently, the activation of CD8+ T lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was impaired compared to HT, IDDM, and the N group; in contrast to the findings with CD4+ T lymphocytes, this was independent of thyroid hormone levels. |
| 290 | 7714099 | On the other hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was impaired compared to the GD and N groups. |
| 291 | 7714099 | In conclusion, the activation of CD8+ T lymphocytes from GD and IDDM by relevant antigens (i.e. |
| 292 | 7714099 | TSHR peptides for GD and GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. |
| 293 | 7714099 | GAD65 for GD and TSHR peptides for IDDM). |
| 294 | 7714099 | There was also a modest stimulation of CD8+ T cells from all groups by tetanus toxoid and cardiac myosin light chain peptide, both irrelevant antigens. |
| 295 | 7714099 | Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. |
| 296 | 7714099 | In this context, we have measured the proliferative responses of peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate decarboxylase (GAD65) by means of 3H thymidine incorporation. |
| 297 | 7714099 | We have also studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow cytometric analysis. |
| 298 | 7714099 | PBMC obtained from 47 patients with Graves' disease (GD) [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM), and 20 normal controls (N), were cultured for 7 days in the presence or absence of the pool peptides representing 3 different segments of TSHR or GAD65 at final concentration of 30 micrograms/mL or 10 micrograms/mL. |
| 299 | 7714099 | The proportion of subjects whose PBMC gave a positive proliferative response with a stimulation index (SI) of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N group. |
| 300 | 7714099 | The CD4+ T lymphocytes from hyper GD group were significantly more activated by TSHR peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to their thyroid hormone levels. |
| 301 | 7714099 | Quite differently, the activation of CD8+ T lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was impaired compared to HT, IDDM, and the N group; in contrast to the findings with CD4+ T lymphocytes, this was independent of thyroid hormone levels. |
| 302 | 7714099 | On the other hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was impaired compared to the GD and N groups. |
| 303 | 7714099 | In conclusion, the activation of CD8+ T lymphocytes from GD and IDDM by relevant antigens (i.e. |
| 304 | 7714099 | TSHR peptides for GD and GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. |
| 305 | 7714099 | GAD65 for GD and TSHR peptides for IDDM). |
| 306 | 7714099 | There was also a modest stimulation of CD8+ T cells from all groups by tetanus toxoid and cardiac myosin light chain peptide, both irrelevant antigens. |
| 307 | 7714099 | Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. |
| 308 | 7714099 | In this context, we have measured the proliferative responses of peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate decarboxylase (GAD65) by means of 3H thymidine incorporation. |
| 309 | 7714099 | We have also studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow cytometric analysis. |
| 310 | 7714099 | PBMC obtained from 47 patients with Graves' disease (GD) [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM), and 20 normal controls (N), were cultured for 7 days in the presence or absence of the pool peptides representing 3 different segments of TSHR or GAD65 at final concentration of 30 micrograms/mL or 10 micrograms/mL. |
| 311 | 7714099 | The proportion of subjects whose PBMC gave a positive proliferative response with a stimulation index (SI) of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N group. |
| 312 | 7714099 | The CD4+ T lymphocytes from hyper GD group were significantly more activated by TSHR peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to their thyroid hormone levels. |
| 313 | 7714099 | Quite differently, the activation of CD8+ T lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was impaired compared to HT, IDDM, and the N group; in contrast to the findings with CD4+ T lymphocytes, this was independent of thyroid hormone levels. |
| 314 | 7714099 | On the other hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was impaired compared to the GD and N groups. |
| 315 | 7714099 | In conclusion, the activation of CD8+ T lymphocytes from GD and IDDM by relevant antigens (i.e. |
| 316 | 7714099 | TSHR peptides for GD and GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. |
| 317 | 7714099 | GAD65 for GD and TSHR peptides for IDDM). |
| 318 | 7714099 | There was also a modest stimulation of CD8+ T cells from all groups by tetanus toxoid and cardiac myosin light chain peptide, both irrelevant antigens. |
| 319 | 7722468 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results in the destruction of the pancreatic islet beta cells. |
| 320 | 7722468 | Glutamic acid decarboxylase (GAD) has been recently indicated as a key autoantigen in the induction of IDDM in nonobese diabetic mice. |
| 321 | 7722468 | GAD65 peptides displaying the human histocompatibility leukocyte antigen (HLA)-A*0201 binding motif have been synthesized. |
| 322 | 7722468 | In three cases (one preclinical IDDM and two recent-onset IDDM), we detected specific killing of autologous antigen-presenting cells when incubated with GAD114-123 peptide or when infected with a recombinant vaccinia virus expressing GAD65. |
| 323 | 7722468 | Our finding suggests that GAD-specific cytotoxic T lymphocytes may play a critical role in the initial events of IDDM. |
| 324 | 7722468 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results in the destruction of the pancreatic islet beta cells. |
| 325 | 7722468 | Glutamic acid decarboxylase (GAD) has been recently indicated as a key autoantigen in the induction of IDDM in nonobese diabetic mice. |
| 326 | 7722468 | GAD65 peptides displaying the human histocompatibility leukocyte antigen (HLA)-A*0201 binding motif have been synthesized. |
| 327 | 7722468 | In three cases (one preclinical IDDM and two recent-onset IDDM), we detected specific killing of autologous antigen-presenting cells when incubated with GAD114-123 peptide or when infected with a recombinant vaccinia virus expressing GAD65. |
| 328 | 7722468 | Our finding suggests that GAD-specific cytotoxic T lymphocytes may play a critical role in the initial events of IDDM. |
| 329 | 7734039 | Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). |
| 330 | 7734039 | Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. |
| 331 | 7734039 | GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. |
| 332 | 7734039 | GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. |
| 333 | 7734039 | GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). |
| 334 | 7734039 | The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. |
| 335 | 7734039 | We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM. |
| 336 | 7734039 | Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). |
| 337 | 7734039 | Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. |
| 338 | 7734039 | GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. |
| 339 | 7734039 | GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. |
| 340 | 7734039 | GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). |
| 341 | 7734039 | The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. |
| 342 | 7734039 | We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM. |
| 343 | 7734039 | Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). |
| 344 | 7734039 | Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. |
| 345 | 7734039 | GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. |
| 346 | 7734039 | GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. |
| 347 | 7734039 | GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). |
| 348 | 7734039 | The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. |
| 349 | 7734039 | We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM. |
| 350 | 7734039 | Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). |
| 351 | 7734039 | Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. |
| 352 | 7734039 | GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. |
| 353 | 7734039 | GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. |
| 354 | 7734039 | GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). |
| 355 | 7734039 | The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. |
| 356 | 7734039 | We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM. |
| 357 | 7734039 | Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). |
| 358 | 7734039 | Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. |
| 359 | 7734039 | GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. |
| 360 | 7734039 | GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. |
| 361 | 7734039 | GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). |
| 362 | 7734039 | The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. |
| 363 | 7734039 | We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM. |
| 364 | 7734039 | Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM). |
| 365 | 7734039 | Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. |
| 366 | 7734039 | GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. |
| 367 | 7734039 | GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. |
| 368 | 7734039 | GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). |
| 369 | 7734039 | The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. |
| 370 | 7734039 | We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM. |
| 371 | 7772701 | Glutamic acid decarboxylase antibodies (GAD65Ab) are common in new onset Caucasian insulin-dependent diabetic (IDDM) patients but it is unclear if this marker is also prevalent in patients of other ethnic backgrounds. |
| 372 | 7772701 | We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non-labelled recombinant human GAD65 (rhGAD65). |
| 373 | 7772701 | Our data are consistent with a strong association of GAD65Ab also in Japanese IDDM, and suggest that, when present, GAD67Ab are frequently directed to epitope(s) common to GAD65 and GAD67. |
| 374 | 7772701 | Glutamic acid decarboxylase antibodies (GAD65Ab) are common in new onset Caucasian insulin-dependent diabetic (IDDM) patients but it is unclear if this marker is also prevalent in patients of other ethnic backgrounds. |
| 375 | 7772701 | We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non-labelled recombinant human GAD65 (rhGAD65). |
| 376 | 7772701 | Our data are consistent with a strong association of GAD65Ab also in Japanese IDDM, and suggest that, when present, GAD67Ab are frequently directed to epitope(s) common to GAD65 and GAD67. |
| 377 | 7783365 | Since it was reported that the 64kD antigen that had been found to be the target of autoantibodies in the sera from IDDM patients was the same as GAD, GAD antibodies have been one of the focuses of many investigations. |
| 378 | 7783365 | To confirm the relevance of pig GAD as the target antigen, we compared the sequences and antigenic activities among pig, rat and recombinant human GAD65. |
| 379 | 7806022 | Furthermore, one of the three islet cell antibody negative individuals who developed IDDM was GAD65 antibody positive both in 1976 and in 1989. |
| 380 | 7809009 | Glutamic acid decarboxylase (GAD) is a candidate target autoantigen involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 381 | 7809009 | Using GAD isoform-specific antibodies in an immunoblot assay, we found that expression of both GAD-65 and GAD-67 in cultured islets was glucose dependent and that increased expression of both forms of GAD correlated with increased functional state of the beta cell. |
| 382 | 7821743 | The clinical onset of insulin-dependent diabetes is associated with several autoimmune phenomena including islet cell antibodies, glutamic acid decarboxylase (the GAD65 isoform) autoantibodies (GAD65Ab) as well as insulin autoantibodies. |
| 383 | 7821743 | The autoreactive sites or epitopes of GAD65 and insulin remain to be determined. |
| 384 | 7821743 | The clinical onset of insulin-dependent diabetes is associated with several autoimmune phenomena including islet cell antibodies, glutamic acid decarboxylase (the GAD65 isoform) autoantibodies (GAD65Ab) as well as insulin autoantibodies. |
| 385 | 7821743 | The autoreactive sites or epitopes of GAD65 and insulin remain to be determined. |
| 386 | 7822765 | Dual immunostaining with GAD isoform-specific antibodies and polyclonal antibodies to glucagon showed that GAD65 was primarily detected in rat pancreatic islet beta-cells, whereas alpha-cells had weak GAD65 staining. |
| 387 | 7822765 | These data demonstrate that antibodies raised against the N-terminus of GAD allow differential immunocytochemical identification of GAD67 and GAD65. |
| 388 | 7822765 | Differential expression of GAD isoforms within islet alpha- and beta-cells supports the role of GAD65 in autoimmune diabetes and stiff-man syndrome. |
| 389 | 7822765 | Dual immunostaining with GAD isoform-specific antibodies and polyclonal antibodies to glucagon showed that GAD65 was primarily detected in rat pancreatic islet beta-cells, whereas alpha-cells had weak GAD65 staining. |
| 390 | 7822765 | These data demonstrate that antibodies raised against the N-terminus of GAD allow differential immunocytochemical identification of GAD67 and GAD65. |
| 391 | 7822765 | Differential expression of GAD isoforms within islet alpha- and beta-cells supports the role of GAD65 in autoimmune diabetes and stiff-man syndrome. |
| 392 | 7822765 | Dual immunostaining with GAD isoform-specific antibodies and polyclonal antibodies to glucagon showed that GAD65 was primarily detected in rat pancreatic islet beta-cells, whereas alpha-cells had weak GAD65 staining. |
| 393 | 7822765 | These data demonstrate that antibodies raised against the N-terminus of GAD allow differential immunocytochemical identification of GAD67 and GAD65. |
| 394 | 7822765 | Differential expression of GAD isoforms within islet alpha- and beta-cells supports the role of GAD65 in autoimmune diabetes and stiff-man syndrome. |
| 395 | 7833679 | In human AITD, recent studies have demonstrated that CD8+ (suppressor/cytotoxic) and CD8+CD11b+ ("pure suppressor") cells are activated by irrelevant antigen normally, but are significantly less well activated in response to thyroglobulin or thyroperoxidase. |
| 396 | 7833679 | In further similar studies, CD8+ cells from patients with Graves' disease (GD) are induced normally in response to glutamic acid decarboxylase-65 (GAD-65), the putative beta cell antigen important in insulin-dependent diabetes mellitus (IDDM), but significantly less to synthetic TSH receptor (TSHR). |
| 397 | 7833679 | Conversely, CD8+ cells from patients with IDDM are activated normally in response to TSHR, but significantly less to GAD-65. |
| 398 | 7833679 | In human AITD, recent studies have demonstrated that CD8+ (suppressor/cytotoxic) and CD8+CD11b+ ("pure suppressor") cells are activated by irrelevant antigen normally, but are significantly less well activated in response to thyroglobulin or thyroperoxidase. |
| 399 | 7833679 | In further similar studies, CD8+ cells from patients with Graves' disease (GD) are induced normally in response to glutamic acid decarboxylase-65 (GAD-65), the putative beta cell antigen important in insulin-dependent diabetes mellitus (IDDM), but significantly less to synthetic TSH receptor (TSHR). |
| 400 | 7833679 | Conversely, CD8+ cells from patients with IDDM are activated normally in response to TSHR, but significantly less to GAD-65. |
| 401 | 7840855 | Type 1 diabetes in man and the NOD (H-2g7) mouse is frequently associated with an autoimmune response to two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. |
| 402 | 7883841 | Patients with adult-onset Type 1 (insulin-dependent) diabetes mellitus (IDDM) are more difficult to identify than young patients, as their clinical onset is often less acute with a questionable state of insulin dependency. |
| 403 | 7883841 | Sera from 312 recent-onset IDDM patients under age 40 and 163 age-matched controls were assayed for IAA, ICA, and antibodies against recombinant GAD65 (M(r) 65,000) or GAD67 (M(r) 67,000). |
| 404 | 7888042 | GAD65 autoantibodies increase the predictability but not the sensitivity of islet cell and insulin autoantibodies for developing insulin dependent diabetes mellitus. |
| 405 | 7926302 | Glutamic acid decarboxylase (GAD65) autoantibodies in prediction of beta-cell function and remission in recent-onset IDDM after cyclosporin treatment. |
| 406 | 7926302 | We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD65 Ab) were affected by cyclosporin therapy and were related to subsequent non-insulin-requiring remission and loss of glucagon-stimulated C-peptide response in 132 recent-onset insulin-dependent diabetes mellitus (IDDM) patients treated with cyclosporin or placebo for 12 months. |
| 407 | 7926302 | GAD65 Ab were found at onset in 66% (87 of 132) of IDDM patients and in 1% (1 of 100) of healthy control subjects. |
| 408 | 7926302 | The presence or absence of GAD65 Ab at study entry did not predict non-insulin-requiring remission in either cyclosporin- or placebo-treated patients. |
| 409 | 7926302 | Glutamic acid decarboxylase (GAD65) autoantibodies in prediction of beta-cell function and remission in recent-onset IDDM after cyclosporin treatment. |
| 410 | 7926302 | We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD65 Ab) were affected by cyclosporin therapy and were related to subsequent non-insulin-requiring remission and loss of glucagon-stimulated C-peptide response in 132 recent-onset insulin-dependent diabetes mellitus (IDDM) patients treated with cyclosporin or placebo for 12 months. |
| 411 | 7926302 | GAD65 Ab were found at onset in 66% (87 of 132) of IDDM patients and in 1% (1 of 100) of healthy control subjects. |
| 412 | 7926302 | The presence or absence of GAD65 Ab at study entry did not predict non-insulin-requiring remission in either cyclosporin- or placebo-treated patients. |
| 413 | 7926302 | Glutamic acid decarboxylase (GAD65) autoantibodies in prediction of beta-cell function and remission in recent-onset IDDM after cyclosporin treatment. |
| 414 | 7926302 | We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD65 Ab) were affected by cyclosporin therapy and were related to subsequent non-insulin-requiring remission and loss of glucagon-stimulated C-peptide response in 132 recent-onset insulin-dependent diabetes mellitus (IDDM) patients treated with cyclosporin or placebo for 12 months. |
| 415 | 7926302 | GAD65 Ab were found at onset in 66% (87 of 132) of IDDM patients and in 1% (1 of 100) of healthy control subjects. |
| 416 | 7926302 | The presence or absence of GAD65 Ab at study entry did not predict non-insulin-requiring remission in either cyclosporin- or placebo-treated patients. |
| 417 | 7926302 | Glutamic acid decarboxylase (GAD65) autoantibodies in prediction of beta-cell function and remission in recent-onset IDDM after cyclosporin treatment. |
| 418 | 7926302 | We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD65 Ab) were affected by cyclosporin therapy and were related to subsequent non-insulin-requiring remission and loss of glucagon-stimulated C-peptide response in 132 recent-onset insulin-dependent diabetes mellitus (IDDM) patients treated with cyclosporin or placebo for 12 months. |
| 419 | 7926302 | GAD65 Ab were found at onset in 66% (87 of 132) of IDDM patients and in 1% (1 of 100) of healthy control subjects. |
| 420 | 7926302 | The presence or absence of GAD65 Ab at study entry did not predict non-insulin-requiring remission in either cyclosporin- or placebo-treated patients. |
| 421 | 7958502 | To test the role of glutamic acid decarboxylase (GAD65) or bovine serum albumin (BSA) autoimmunity in the pathogenesis of diabetes, GAD65 or BSA was injected intraperitoneally into neonatal female NOD mice (100 micrograms/mouse of each protein). |
| 422 | 7964474 | We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. |
| 423 | 7964474 | We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. |
| 424 | 7964474 | Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM. |
| 425 | 7964474 | We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. |
| 426 | 7964474 | We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. |
| 427 | 7964474 | Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM. |
| 428 | 7964474 | We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. |
| 429 | 7964474 | We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. |
| 430 | 7964474 | Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM. |
| 431 | 8034738 | In this study we have investigated the targeting signal of the 65-kD isoform of glutamic acid decarboxylase (GAD65), a major autoantigen in two autoimmune diseases: Stiff-Man syndrome and insulin-dependent diabetes mellitus. |
| 432 | 8063033 | Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. |
| 433 | 8063033 | One set of IDDM patient (n = 10) and control (n = 50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. |
| 434 | 8063033 | In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. |
| 435 | 8063033 | Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methionine-labelled recombinant GAD. |
| 436 | 8063033 | Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. |
| 437 | 8063033 | One set of IDDM patient (n = 10) and control (n = 50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. |
| 438 | 8063033 | In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. |
| 439 | 8063033 | Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methionine-labelled recombinant GAD. |
| 440 | 8063033 | Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. |
| 441 | 8063033 | One set of IDDM patient (n = 10) and control (n = 50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. |
| 442 | 8063033 | In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. |
| 443 | 8063033 | Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methionine-labelled recombinant GAD. |
| 444 | 8070615 | Immune reactivity to the enzyme glutamic acid decarboxylase (GAD), a pancreatic islet autoantigen, is present at the diagnosis of insulin-dependent diabetes mellitus (IDDM). |
| 445 | 8070615 | Because GAD is also highly expressed in the nervous system, we investigated the presence of autoantibodies to the isoform GAD65 in patients with diabetic neuropathy, which is a debilitating complication of the disease. |
| 446 | 8100786 | The NOD mouse may have as many as 10 susceptibility genes, including its novel IA major histocompatibility complex antigen and a defective interferon-gamma receptor, whereas human IDDM is so far known to be encoded by cis and trans complementation products of certain DQ genes on chromosome 6q, and a gene in the insulin-like growth factor II region on chromosome 11p. |
| 447 | 8100786 | Islet cell antibody negative siblings of IDDM patients appear to have lower than expected abilities to secrete insulin in response to intravenous glucose. |
| 448 | 8100786 | Sera from patients before and/or after developing IDDM immunoprecipitate two native proteins of 64,000- and 38,000-M(r) glutamic acid decarboxylase (GAD65) reacting to conformational epitopes. |
| 449 | 8100786 | It can be induced by as disparate means as tuberculin antigen administration, by interleukin-4 treatments, by transfer of T-cell lines generated in autologous mixed lymphocyte responses, and by immunization to insulin B-chain, whereas oral islet cell antigens, such as insulin, can delay diabetes onset in the NOD mouse. |
| 450 | 8149657 | In the present study the reactivity of sera from 34 prediabetic and 15 diabetic NOD mice was tested against GAD protein present in islets of Langerhans and cerebellum, and against recombinant, semi-purified GAD-65 and GAD-67. |
| 451 | 8168635 | The autoimmune response that leads to destruction of pancreatic islet beta-cells and insulin-dependent diabetes mellitus (IDDM) has a genetic basis; however, environmental factors can exert profound modulating effects on the genetic predisposition to this autoimmune response. |
| 452 | 8168635 | Thus, recent studies in NOD mice suggest that the islet beta-cell-directed autoimmune response may be mediated by a T-helper 1 (Th1) subset of T-cells producing the cytokines interleukin-2 (IL-2) and interferon-gamma. |
| 453 | 8168635 | These studies also suggest that the diabetes-protective effects of administering microbial agents, adjuvants, and a beta-cell autoantigen (GAD65 [glutamic acid decarboxylase]) may result from activation of a Th2 subset of T-cells that produce the cytokines IL-4 and IL-10 and consequently downregulate the Th1-cell-mediated autoimmune response. |
| 454 | 8232539 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by lymphocytic infiltration of the islets of Langerhans (insulitis) and destruction of insulin-secreting pancreatic beta-cells. |
| 455 | 8232539 | Furthermore, NOD mice receiving intrathymic injections of GAD65 exhibit markedly reduced T-cell proliferative responses to GAD and to the rest of the panel, in addition to remaining free of diabetes. |
| 456 | 8240659 | The 64,000-M(r) (64K) islet autoantigen, which is considered to be a target protein of beta cell destruction in insulin-dependent diabetes mellitus (IDDM), has recently been identified as the enzyme glutamic acid decarboxylase (GAD). |
| 457 | 8240659 | Both GADs are also present in the infected mice brain at 72 h p.i.; however, their islets contain about three-fold more GAD65, and essentially no detectable GAD67. |
| 458 | 8245784 | It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus. |
| 459 | 8245784 | The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes. |
| 460 | 8245784 | This reactivity is similar to that displayed by the monoclonal antibody GAD 6, suggesting the presence of a single immunodominant epitope (SMS-E1) in this region of GAD-65. |
| 461 | 8245784 | In addition, most SMS sera recognized at least one epitope (SMS-E2) in the NH2-terminal domain of GAD-65 (amino acids 1-95). |
| 462 | 8245784 | The demonstration in SMS patients of a strikingly homogeneous humoral autoimmune response against GAD and the identification of dominant autoreactive target regions may help to elucidate the molecular mechanisms of GAD processing and presentation involved in GAD autoimmunity. |
| 463 | 8245784 | Moreover, the reactivity reported here of GAD autoantibodies in SMS partially differs from the reactivity of GAD autoantibodies in insulin-dependent diabetes mellitus, suggesting a link between the pattern of humoral autoimmunity and the clinical condition. |
| 464 | 8245784 | It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus. |
| 465 | 8245784 | The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes. |
| 466 | 8245784 | This reactivity is similar to that displayed by the monoclonal antibody GAD 6, suggesting the presence of a single immunodominant epitope (SMS-E1) in this region of GAD-65. |
| 467 | 8245784 | In addition, most SMS sera recognized at least one epitope (SMS-E2) in the NH2-terminal domain of GAD-65 (amino acids 1-95). |
| 468 | 8245784 | The demonstration in SMS patients of a strikingly homogeneous humoral autoimmune response against GAD and the identification of dominant autoreactive target regions may help to elucidate the molecular mechanisms of GAD processing and presentation involved in GAD autoimmunity. |
| 469 | 8245784 | Moreover, the reactivity reported here of GAD autoantibodies in SMS partially differs from the reactivity of GAD autoantibodies in insulin-dependent diabetes mellitus, suggesting a link between the pattern of humoral autoimmunity and the clinical condition. |
| 470 | 8245784 | It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus. |
| 471 | 8245784 | The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes. |
| 472 | 8245784 | This reactivity is similar to that displayed by the monoclonal antibody GAD 6, suggesting the presence of a single immunodominant epitope (SMS-E1) in this region of GAD-65. |
| 473 | 8245784 | In addition, most SMS sera recognized at least one epitope (SMS-E2) in the NH2-terminal domain of GAD-65 (amino acids 1-95). |
| 474 | 8245784 | The demonstration in SMS patients of a strikingly homogeneous humoral autoimmune response against GAD and the identification of dominant autoreactive target regions may help to elucidate the molecular mechanisms of GAD processing and presentation involved in GAD autoimmunity. |
| 475 | 8245784 | Moreover, the reactivity reported here of GAD autoantibodies in SMS partially differs from the reactivity of GAD autoantibodies in insulin-dependent diabetes mellitus, suggesting a link between the pattern of humoral autoimmunity and the clinical condition. |
| 476 | 8314014 | Insulin, carboxypeptidase-H (CP-H), and glutamate decarboxylase (GAD) have been identified as potential autoantigens in insulin-dependent diabetes mellitus (IDDM). |
| 477 | 8314014 | In contrast, islet cells failed to reveal cell-surface staining for GAD65, another putative autoantigen in IDDM, under either basal or insulin stimulatory conditions or following exposure of islet cells to the cytokines interleukin-1 beta, tumor necrosis factor-alpha, and recombinant human interferon-gamma. |
| 478 | 8314020 | Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). |
| 479 | 8314020 | By using this assay, 77% (77 of 100) of serum samples from recent-onset IDDM patients were positive for GAD65 antibodies compared with 4% (4 of 100) of serum samples from healthy control subjects. |
| 480 | 8314020 | In competition analysis with unlabeled purified recombinant human islet GAD65, binding to tracer was inhibited in 74% (74 of 100) of the GAD65-positive IDDM serum samples compared with 2% of the control samples. |
| 481 | 8314020 | The frequency of GAD antibodies was significantly higher with IDDM onset before the age of 30 (80%, 59 of 74) than after the age of 30 (48%, 10 of 21) (P < 0.01). |
| 482 | 8314020 | In conclusion, even large numbers of serum samples can now be tested for GAD65 antibodies in a relatively short time, allowing screening of individuals without a family history of IDDM for the presence of this marker. |
| 483 | 8314020 | Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). |
| 484 | 8314020 | By using this assay, 77% (77 of 100) of serum samples from recent-onset IDDM patients were positive for GAD65 antibodies compared with 4% (4 of 100) of serum samples from healthy control subjects. |
| 485 | 8314020 | In competition analysis with unlabeled purified recombinant human islet GAD65, binding to tracer was inhibited in 74% (74 of 100) of the GAD65-positive IDDM serum samples compared with 2% of the control samples. |
| 486 | 8314020 | The frequency of GAD antibodies was significantly higher with IDDM onset before the age of 30 (80%, 59 of 74) than after the age of 30 (48%, 10 of 21) (P < 0.01). |
| 487 | 8314020 | In conclusion, even large numbers of serum samples can now be tested for GAD65 antibodies in a relatively short time, allowing screening of individuals without a family history of IDDM for the presence of this marker. |
| 488 | 8314020 | Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). |
| 489 | 8314020 | By using this assay, 77% (77 of 100) of serum samples from recent-onset IDDM patients were positive for GAD65 antibodies compared with 4% (4 of 100) of serum samples from healthy control subjects. |
| 490 | 8314020 | In competition analysis with unlabeled purified recombinant human islet GAD65, binding to tracer was inhibited in 74% (74 of 100) of the GAD65-positive IDDM serum samples compared with 2% of the control samples. |
| 491 | 8314020 | The frequency of GAD antibodies was significantly higher with IDDM onset before the age of 30 (80%, 59 of 74) than after the age of 30 (48%, 10 of 21) (P < 0.01). |
| 492 | 8314020 | In conclusion, even large numbers of serum samples can now be tested for GAD65 antibodies in a relatively short time, allowing screening of individuals without a family history of IDDM for the presence of this marker. |
| 493 | 8376591 | We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). |
| 494 | 8376591 | In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. |
| 495 | 8376591 | After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). |
| 496 | 8376591 | An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). |
| 497 | 8376591 | In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. |
| 498 | 8376591 | Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. |
| 499 | 8376591 | We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). |
| 500 | 8376591 | In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. |
| 501 | 8376591 | After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). |
| 502 | 8376591 | An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). |
| 503 | 8376591 | In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. |
| 504 | 8376591 | Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. |
| 505 | 8376591 | We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). |
| 506 | 8376591 | In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. |
| 507 | 8376591 | After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). |
| 508 | 8376591 | An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). |
| 509 | 8376591 | In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. |
| 510 | 8376591 | Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. |
| 511 | 8376591 | We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). |
| 512 | 8376591 | In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. |
| 513 | 8376591 | After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). |
| 514 | 8376591 | An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). |
| 515 | 8376591 | In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. |
| 516 | 8376591 | Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. |
| 517 | 8376591 | We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). |
| 518 | 8376591 | In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. |
| 519 | 8376591 | After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). |
| 520 | 8376591 | An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). |
| 521 | 8376591 | In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. |
| 522 | 8376591 | Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. |
| 523 | 8376591 | We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). |
| 524 | 8376591 | In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. |
| 525 | 8376591 | After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). |
| 526 | 8376591 | An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). |
| 527 | 8376591 | In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. |
| 528 | 8376591 | Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. |
| 529 | 8405707 | This was achieved 1) by preabsorption of ICA+ sera with recombinant GAD65 and/or GAD67 expressed in a baculovirus system and 2) by ICA analysis of sera on mouse pancreas, as GAD antibodies do not stain mouse islets in the immunofluorescence test. |
| 530 | 8423232 | At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). |
| 531 | 8423232 | Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. |
| 532 | 8464926 | GAD-65 is a dominant autoantigen in stiff-man syndrome and insulin-dependent diabetes mellitus. |
| 533 | 8486775 | Sera from 38 patients with type 1 (insulin-dependent) diabetes mellitus, which precipitated a 64-kD antigen from rat islets, reacted with recombinant GAD-65 in relation to their anti-64-kD titers. |
| 534 | 8486775 | Subsequently, [35S]methionine-labeled GAD-65 was purified from COS cell lysates and employed in a binding assay with 50 sera of patients with recent onset of type 1 diabetes mellitus. 38 sera (76%) precipitated labeled GAD-65 with titers that correlated with islet cell antibodies (ICA), determined in a standard immunofluorescence assay. 2 sera were GAD positive but ICA negative, 4 were positive only for ICA, and 6 were negative for both GAD and ICA, as were the sera of 20 controls. |
| 535 | 8486775 | Sera from 38 patients with type 1 (insulin-dependent) diabetes mellitus, which precipitated a 64-kD antigen from rat islets, reacted with recombinant GAD-65 in relation to their anti-64-kD titers. |
| 536 | 8486775 | Subsequently, [35S]methionine-labeled GAD-65 was purified from COS cell lysates and employed in a binding assay with 50 sera of patients with recent onset of type 1 diabetes mellitus. 38 sera (76%) precipitated labeled GAD-65 with titers that correlated with islet cell antibodies (ICA), determined in a standard immunofluorescence assay. 2 sera were GAD positive but ICA negative, 4 were positive only for ICA, and 6 were negative for both GAD and ICA, as were the sera of 20 controls. |
| 537 | 8504767 | We, therefore, tested hypotheses that M. nemestrina islets also have restricted GAD expression, that GAD expression in primates is stimulated by glucose, and that this stimulation remains restricted to the 64,000 mol wt (GAD65) isoform. |
| 538 | 8507202 | Glutamic acid decarboxylase (GAD) is a pancreatic islet autoantigen in insulin-dependent diabetes (IDD). |
| 539 | 8507202 | Two forms of GAD, GAD65 and GAD67, have been identified in brain but human islets have been reported to express only GAD65. |
| 540 | 8507202 | The presence of GAD67 in human pancreas implies that this form of GAD, as well as GAD65, has a pathogenic role in IDD. |
| 541 | 8507202 | Glutamic acid decarboxylase (GAD) is a pancreatic islet autoantigen in insulin-dependent diabetes (IDD). |
| 542 | 8507202 | Two forms of GAD, GAD65 and GAD67, have been identified in brain but human islets have been reported to express only GAD65. |
| 543 | 8507202 | The presence of GAD67 in human pancreas implies that this form of GAD, as well as GAD65, has a pathogenic role in IDD. |
| 544 | 8552991 | In vitro stimulation with glutamic acid decarboxylase (GAD65) leads to an oligoclonal response of peripheral T-cells in an IDDM patient. |
| 545 | 8552991 | The enzyme glutamic acid decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 546 | 8552991 | To study T-cell reactivity towards GAD, peripheral blood leucocytes from seven patients with IDDM and five control subjects were stimulated in vitro with recombinant GAD. |
| 547 | 8552991 | The author's data suggest that GAD-reactive T-cells of Th1 phenotype can be obtained after in vitro stimulation of peripheral blood leucocytes from an HLA-DRB1*03/*04 heterozygous IDDM patient. |
| 548 | 8552991 | In vitro stimulation with glutamic acid decarboxylase (GAD65) leads to an oligoclonal response of peripheral T-cells in an IDDM patient. |
| 549 | 8552991 | The enzyme glutamic acid decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 550 | 8552991 | To study T-cell reactivity towards GAD, peripheral blood leucocytes from seven patients with IDDM and five control subjects were stimulated in vitro with recombinant GAD. |
| 551 | 8552991 | The author's data suggest that GAD-reactive T-cells of Th1 phenotype can be obtained after in vitro stimulation of peripheral blood leucocytes from an HLA-DRB1*03/*04 heterozygous IDDM patient. |
| 552 | 8566695 | Auto-antibodies to GAD65 have been associated with the onset of insulin-dependent diabetes mellitus. |
| 553 | 8595722 | DELISA: sensitive nonisotopic assay for GAD65 autoantibodies, a key risk-assessment marker for insulin-dependent diabetes mellitus. |
| 554 | 8603772 | One of the major beta-cell autoantigens associated with IDDM is GAD. |
| 555 | 8603772 | We therefore analyzed patterns of GAD gene transcription by quantitating the mRNAs encoding both the 65- and 67-kDa isoforms (GAD65 and GAD67, respectively) in human fetal, postnatal, and adult pancreases, as well as in isolated adult islets, and examined their tissue-specific expression. |
| 556 | 8603772 | In the fetal pancreas, strong immunoreactivity for GAD65 was also evident in epithelial cells, which lacked expression of insulin or glucagon, some of which were present in the ductal epithelium, suggesting that GAD65 expression might correlate with endocrine determination. |
| 557 | 8603772 | One of the major beta-cell autoantigens associated with IDDM is GAD. |
| 558 | 8603772 | We therefore analyzed patterns of GAD gene transcription by quantitating the mRNAs encoding both the 65- and 67-kDa isoforms (GAD65 and GAD67, respectively) in human fetal, postnatal, and adult pancreases, as well as in isolated adult islets, and examined their tissue-specific expression. |
| 559 | 8603772 | In the fetal pancreas, strong immunoreactivity for GAD65 was also evident in epithelial cells, which lacked expression of insulin or glucagon, some of which were present in the ductal epithelium, suggesting that GAD65 expression might correlate with endocrine determination. |
| 560 | 8635655 | We analyzed peripheral blood mononuclear cell (PBMC) responses to human insulin, glutamate decarboxylase GAD65, tyrosine phosphatase ICA512, glucagon, membrane preparations of RIN cells and human pancreas, and three control antigens (La = nuclear cell antigen, tetanus toxoid, and phytohemagglutinin). |
| 561 | 8635655 | The highest differences in the magnitude of proliferative responses were seen for ICA512, followed by membrane preparations of RIN cells, GAD65, and human pancreas. |
| 562 | 8635655 | We analyzed peripheral blood mononuclear cell (PBMC) responses to human insulin, glutamate decarboxylase GAD65, tyrosine phosphatase ICA512, glucagon, membrane preparations of RIN cells and human pancreas, and three control antigens (La = nuclear cell antigen, tetanus toxoid, and phytohemagglutinin). |
| 563 | 8635655 | The highest differences in the magnitude of proliferative responses were seen for ICA512, followed by membrane preparations of RIN cells, GAD65, and human pancreas. |
| 564 | 8636356 | To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. |
| 565 | 8636356 | GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell antibodies, and HLA-DQA1, -DQB1, and -DRB1 were analyzed in relation to IDDM or a decreased insulin secretory capacity. |
| 566 | 8666914 | Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. |
| 567 | 8666914 | Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). |
| 568 | 8666914 | Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. |
| 569 | 8666914 | GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. |
| 570 | 8666914 | Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. |
| 571 | 8666914 | Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. |
| 572 | 8666914 | Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. |
| 573 | 8666914 | Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). |
| 574 | 8666914 | Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. |
| 575 | 8666914 | GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. |
| 576 | 8666914 | Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. |
| 577 | 8666914 | Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. |
| 578 | 8666914 | Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. |
| 579 | 8666914 | Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). |
| 580 | 8666914 | Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. |
| 581 | 8666914 | GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. |
| 582 | 8666914 | Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. |
| 583 | 8666914 | Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. |
| 584 | 8666914 | Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. |
| 585 | 8666914 | Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). |
| 586 | 8666914 | Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. |
| 587 | 8666914 | GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. |
| 588 | 8666914 | Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. |
| 589 | 8666914 | Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. |
| 590 | 8666914 | Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. |
| 591 | 8666914 | Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). |
| 592 | 8666914 | Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. |
| 593 | 8666914 | GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. |
| 594 | 8666914 | Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. |
| 595 | 8666914 | Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. |
| 596 | 8666914 | Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. |
| 597 | 8666914 | Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). |
| 598 | 8666914 | Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. |
| 599 | 8666914 | GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. |
| 600 | 8666914 | Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. |
| 601 | 8666914 | Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. |
| 602 | 8675688 | Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. |
| 603 | 8675688 | Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. |
| 604 | 8675688 | The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. |
| 605 | 8675688 | The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. |
| 606 | 8675688 | GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes. |
| 607 | 8675688 | Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. |
| 608 | 8675688 | Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. |
| 609 | 8675688 | The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. |
| 610 | 8675688 | The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. |
| 611 | 8675688 | GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes. |
| 612 | 8675688 | Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. |
| 613 | 8675688 | Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. |
| 614 | 8675688 | The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. |
| 615 | 8675688 | The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. |
| 616 | 8675688 | GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes. |
| 617 | 8675688 | Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. |
| 618 | 8675688 | Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. |
| 619 | 8675688 | The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. |
| 620 | 8675688 | The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. |
| 621 | 8675688 | GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes. |
| 622 | 8675688 | Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. |
| 623 | 8675688 | Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. |
| 624 | 8675688 | The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. |
| 625 | 8675688 | The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. |
| 626 | 8675688 | GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes. |
| 627 | 8679901 | Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus. |
| 628 | 8679901 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 629 | 8679901 | The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. |
| 630 | 8679901 | To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. |
| 631 | 8679901 | This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. |
| 632 | 8679901 | The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. |
| 633 | 8679901 | No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM. |
| 634 | 8679901 | Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus. |
| 635 | 8679901 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 636 | 8679901 | The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. |
| 637 | 8679901 | To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. |
| 638 | 8679901 | This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. |
| 639 | 8679901 | The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. |
| 640 | 8679901 | No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM. |
| 641 | 8679901 | Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus. |
| 642 | 8679901 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 643 | 8679901 | The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. |
| 644 | 8679901 | To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. |
| 645 | 8679901 | This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. |
| 646 | 8679901 | The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. |
| 647 | 8679901 | No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM. |
| 648 | 8679901 | Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus. |
| 649 | 8679901 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 650 | 8679901 | The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. |
| 651 | 8679901 | To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. |
| 652 | 8679901 | This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. |
| 653 | 8679901 | The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. |
| 654 | 8679901 | No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM. |
| 655 | 8679901 | Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus. |
| 656 | 8679901 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 657 | 8679901 | The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. |
| 658 | 8679901 | To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. |
| 659 | 8679901 | This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. |
| 660 | 8679901 | The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. |
| 661 | 8679901 | No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM. |
| 662 | 8679901 | Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus. |
| 663 | 8679901 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 664 | 8679901 | The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. |
| 665 | 8679901 | To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. |
| 666 | 8679901 | This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. |
| 667 | 8679901 | The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. |
| 668 | 8679901 | No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM. |
| 669 | 8689840 | Insulin-dependent diabetes mellitus (IDDM) is linked to HLA factors on human chromosome 6 and strongly associated with the presence of autoantibodies against the glutamic acid decarboxylase isoform GAD65. |
| 670 | 8689840 | At the same time, the molecular cloning of human islet GAD65 and the development of precise and reproducible GAD65Ab assays with recombinant human GAD65 has given new insights to the problem of to what extent HLA control the development of a GAD65 immune response or to the development of IDDM. |
| 671 | 8689840 | This is important since other factors may control the development of IDDM in only a fraction of GAD65 antibody positive individuals detected following a screening of the general population. |
| 672 | 8689840 | Insulin-dependent diabetes mellitus (IDDM) is linked to HLA factors on human chromosome 6 and strongly associated with the presence of autoantibodies against the glutamic acid decarboxylase isoform GAD65. |
| 673 | 8689840 | At the same time, the molecular cloning of human islet GAD65 and the development of precise and reproducible GAD65Ab assays with recombinant human GAD65 has given new insights to the problem of to what extent HLA control the development of a GAD65 immune response or to the development of IDDM. |
| 674 | 8689840 | This is important since other factors may control the development of IDDM in only a fraction of GAD65 antibody positive individuals detected following a screening of the general population. |
| 675 | 8689840 | Insulin-dependent diabetes mellitus (IDDM) is linked to HLA factors on human chromosome 6 and strongly associated with the presence of autoantibodies against the glutamic acid decarboxylase isoform GAD65. |
| 676 | 8689840 | At the same time, the molecular cloning of human islet GAD65 and the development of precise and reproducible GAD65Ab assays with recombinant human GAD65 has given new insights to the problem of to what extent HLA control the development of a GAD65 immune response or to the development of IDDM. |
| 677 | 8689840 | This is important since other factors may control the development of IDDM in only a fraction of GAD65 antibody positive individuals detected following a screening of the general population. |
| 678 | 8692821 | IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. |
| 679 | 8692821 | Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. |
| 680 | 8692821 | Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. |
| 681 | 8692821 | Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. |
| 682 | 8692821 | A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. |
| 683 | 8692821 | It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. |
| 684 | 8692821 | Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening. |
| 685 | 8692821 | IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. |
| 686 | 8692821 | Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. |
| 687 | 8692821 | Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. |
| 688 | 8692821 | Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. |
| 689 | 8692821 | A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. |
| 690 | 8692821 | It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. |
| 691 | 8692821 | Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening. |
| 692 | 8692821 | IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. |
| 693 | 8692821 | Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. |
| 694 | 8692821 | Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. |
| 695 | 8692821 | Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. |
| 696 | 8692821 | A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. |
| 697 | 8692821 | It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. |
| 698 | 8692821 | Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening. |
| 699 | 8692821 | IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. |
| 700 | 8692821 | Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. |
| 701 | 8692821 | Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. |
| 702 | 8692821 | Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. |
| 703 | 8692821 | A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. |
| 704 | 8692821 | It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. |
| 705 | 8692821 | Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening. |
| 706 | 8692821 | IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. |
| 707 | 8692821 | Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. |
| 708 | 8692821 | Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. |
| 709 | 8692821 | Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. |
| 710 | 8692821 | A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. |
| 711 | 8692821 | It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. |
| 712 | 8692821 | Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening. |
| 713 | 8706342 | Glutamic acid decarboxylase (GAD) could be a key antigen involved in this disease, and GAD65 peptide 524-543 has been implicated in early T cell response in young NOD mice. |
| 714 | 8706342 | After peptide challenge of splenocytes in vitro, protection against CY-accelerated diabetes was associated with higher peptide-specific production of T helper type 2 (Th2)-associated interleukins 4 and 10, whereas Th1-associated interferon-gamma and IL-2 were proportionally less represented. |
| 715 | 8706342 | It is concluded that immunization of NOD mice with GAD65 peptide 524-543 can counteract CY-accelerated diabetes, possibly through active cellular suppression linked to a shift of Th1/Th2 balance toward the production of Th2 cytokines such as IL-4 and IL-10. |
| 716 | 8706342 | Glutamic acid decarboxylase (GAD) could be a key antigen involved in this disease, and GAD65 peptide 524-543 has been implicated in early T cell response in young NOD mice. |
| 717 | 8706342 | After peptide challenge of splenocytes in vitro, protection against CY-accelerated diabetes was associated with higher peptide-specific production of T helper type 2 (Th2)-associated interleukins 4 and 10, whereas Th1-associated interferon-gamma and IL-2 were proportionally less represented. |
| 718 | 8706342 | It is concluded that immunization of NOD mice with GAD65 peptide 524-543 can counteract CY-accelerated diabetes, possibly through active cellular suppression linked to a shift of Th1/Th2 balance toward the production of Th2 cytokines such as IL-4 and IL-10. |
| 719 | 8730438 | Antibodies to glutamic acid decarboxylase (GAD), a pancreatic islet beta-cell antigen, are present in > 80% of newly diagnosed insulin-dependent diabetes mellitus (IDDM), and are found in nonobese diabetic (NOD) mice, a murine model of spontaneous IDDM. |
| 720 | 8730438 | To determine whether GAD is a target antigen in the kidney damage of NOD mice, we studied GAD mRNAs (GAD65 and GAD67) by RT-PCR in mesangial cells, isolated glomeruli, and kidney cortex and medulla in NOD and SJL/C57BL mice. |
| 721 | 8734572 | Based on studies in spontaneously non-obese diabetic (NOD) mice, it has been suggested that the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) is of major importance in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 722 | 8734572 | In humans, antibodies to GAD65 are present before and at onset of the disease and in vitro T cell reactivity to GAD has also been reported. |
| 723 | 8734572 | To further characterize the T cell recognition of GAD65, we incubated peripheral blood mononuclear cells from 45 newly diagnosed IDDM patients with purified recombinant human islet GAD65 and correlated the proliferative response with HLA DR haplotype and the presence of GAD65 autoantibodies. |
| 724 | 8734572 | In conclusion, we find a proliferative T cell response to GAD65 in approximately 50% of recent onset IDDM patients and unexpectedly find the majority of responders to be HLA non-DR 3/4 heterozygous patients. |
| 725 | 8734572 | Based on studies in spontaneously non-obese diabetic (NOD) mice, it has been suggested that the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) is of major importance in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 726 | 8734572 | In humans, antibodies to GAD65 are present before and at onset of the disease and in vitro T cell reactivity to GAD has also been reported. |
| 727 | 8734572 | To further characterize the T cell recognition of GAD65, we incubated peripheral blood mononuclear cells from 45 newly diagnosed IDDM patients with purified recombinant human islet GAD65 and correlated the proliferative response with HLA DR haplotype and the presence of GAD65 autoantibodies. |
| 728 | 8734572 | In conclusion, we find a proliferative T cell response to GAD65 in approximately 50% of recent onset IDDM patients and unexpectedly find the majority of responders to be HLA non-DR 3/4 heterozygous patients. |
| 729 | 8734572 | Based on studies in spontaneously non-obese diabetic (NOD) mice, it has been suggested that the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) is of major importance in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 730 | 8734572 | In humans, antibodies to GAD65 are present before and at onset of the disease and in vitro T cell reactivity to GAD has also been reported. |
| 731 | 8734572 | To further characterize the T cell recognition of GAD65, we incubated peripheral blood mononuclear cells from 45 newly diagnosed IDDM patients with purified recombinant human islet GAD65 and correlated the proliferative response with HLA DR haplotype and the presence of GAD65 autoantibodies. |
| 732 | 8734572 | In conclusion, we find a proliferative T cell response to GAD65 in approximately 50% of recent onset IDDM patients and unexpectedly find the majority of responders to be HLA non-DR 3/4 heterozygous patients. |
| 733 | 8734572 | Based on studies in spontaneously non-obese diabetic (NOD) mice, it has been suggested that the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) is of major importance in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 734 | 8734572 | In humans, antibodies to GAD65 are present before and at onset of the disease and in vitro T cell reactivity to GAD has also been reported. |
| 735 | 8734572 | To further characterize the T cell recognition of GAD65, we incubated peripheral blood mononuclear cells from 45 newly diagnosed IDDM patients with purified recombinant human islet GAD65 and correlated the proliferative response with HLA DR haplotype and the presence of GAD65 autoantibodies. |
| 736 | 8734572 | In conclusion, we find a proliferative T cell response to GAD65 in approximately 50% of recent onset IDDM patients and unexpectedly find the majority of responders to be HLA non-DR 3/4 heterozygous patients. |
| 737 | 8739307 | An ELISA displacement test using two biotinylated monoclonals recognizing a linear (M61/7E11) or a conformational GAD65 epitope (M65/6B12) was performed to identify epitope regions recognized by monoclonal GAD antibodies. |
| 738 | 8739307 | The GAD binding by monoclonal GAD antibodies was tested by immunofluorescence on fixed and unfixed pancreatic sections of human, rat, and mouse, and by Dot-blot experiments. 16/23 (69.6%) of the monoclonals were specifically reactive with GAD65 and 7/23 (30.4%) were reactive with both GAD isoforms. 8/16 (50%) of monoclonal GAD65 antibodies recognized a linear GAD epitope located at the N-terminus (pattern 1). 5/16 (31.3%) displaced M65/6B12, indicating the recognition of a conformational GAD epitope (pattern 2). |
| 739 | 8739307 | In conclusion, GAD antibodies recognizing both conformational and linear epitopes of the GAD65 molecule are involved in ICA binding with strong reactivity. |
| 740 | 8739307 | An ELISA displacement test using two biotinylated monoclonals recognizing a linear (M61/7E11) or a conformational GAD65 epitope (M65/6B12) was performed to identify epitope regions recognized by monoclonal GAD antibodies. |
| 741 | 8739307 | The GAD binding by monoclonal GAD antibodies was tested by immunofluorescence on fixed and unfixed pancreatic sections of human, rat, and mouse, and by Dot-blot experiments. 16/23 (69.6%) of the monoclonals were specifically reactive with GAD65 and 7/23 (30.4%) were reactive with both GAD isoforms. 8/16 (50%) of monoclonal GAD65 antibodies recognized a linear GAD epitope located at the N-terminus (pattern 1). 5/16 (31.3%) displaced M65/6B12, indicating the recognition of a conformational GAD epitope (pattern 2). |
| 742 | 8739307 | In conclusion, GAD antibodies recognizing both conformational and linear epitopes of the GAD65 molecule are involved in ICA binding with strong reactivity. |
| 743 | 8739307 | An ELISA displacement test using two biotinylated monoclonals recognizing a linear (M61/7E11) or a conformational GAD65 epitope (M65/6B12) was performed to identify epitope regions recognized by monoclonal GAD antibodies. |
| 744 | 8739307 | The GAD binding by monoclonal GAD antibodies was tested by immunofluorescence on fixed and unfixed pancreatic sections of human, rat, and mouse, and by Dot-blot experiments. 16/23 (69.6%) of the monoclonals were specifically reactive with GAD65 and 7/23 (30.4%) were reactive with both GAD isoforms. 8/16 (50%) of monoclonal GAD65 antibodies recognized a linear GAD epitope located at the N-terminus (pattern 1). 5/16 (31.3%) displaced M65/6B12, indicating the recognition of a conformational GAD epitope (pattern 2). |
| 745 | 8739307 | In conclusion, GAD antibodies recognizing both conformational and linear epitopes of the GAD65 molecule are involved in ICA binding with strong reactivity. |
| 746 | 8743289 | Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). |
| 747 | 8743289 | We derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots. |
| 748 | 8743289 | A sequence homology with human heat shock protein 60 (HSP60) maps to this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. |
| 749 | 8743289 | Our data demonstrate that reactivity of an antibody in Western blots does not necessarily define a classic linear epitope of 6-8 amino acids and describe a new autoreactive epitope in GAD65 different from those reported for sera from patients with SMS. |
| 750 | 8743289 | Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). |
| 751 | 8743289 | We derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots. |
| 752 | 8743289 | A sequence homology with human heat shock protein 60 (HSP60) maps to this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. |
| 753 | 8743289 | Our data demonstrate that reactivity of an antibody in Western blots does not necessarily define a classic linear epitope of 6-8 amino acids and describe a new autoreactive epitope in GAD65 different from those reported for sera from patients with SMS. |
| 754 | 8743289 | Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). |
| 755 | 8743289 | We derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots. |
| 756 | 8743289 | A sequence homology with human heat shock protein 60 (HSP60) maps to this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. |
| 757 | 8743289 | Our data demonstrate that reactivity of an antibody in Western blots does not necessarily define a classic linear epitope of 6-8 amino acids and describe a new autoreactive epitope in GAD65 different from those reported for sera from patients with SMS. |
| 758 | 8743289 | Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). |
| 759 | 8743289 | We derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots. |
| 760 | 8743289 | A sequence homology with human heat shock protein 60 (HSP60) maps to this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. |
| 761 | 8743289 | Our data demonstrate that reactivity of an antibody in Western blots does not necessarily define a classic linear epitope of 6-8 amino acids and describe a new autoreactive epitope in GAD65 different from those reported for sera from patients with SMS. |
| 762 | 8746789 | Recombinant human transforming growth factor beta does not inhibit the effects of interleukin-1 beta on pancreatic islet cells. |
| 763 | 8746789 | The macrophage-derived cytokine, interleukin-1 beta (IL-1 beta), has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct cytotoxicity, and alteration of islet cell antigen expression. |
| 764 | 8746789 | Because transforming growth factor beta (TGF-beta) has been reported to inhibit IL-1 receptor expression in several lymphoid and progenitor cell lines, to induce IL-1 receptor antagonist protein (IRAP) production in human peripheral blood monocytes, and to antagonize several effects of inflammatory cytokines and because oral tolerance may be mediated in part by TGF-beta released by regulatory T lymphocytes, we investigated whether TGF-beta counteracted the effects of IL-1 beta on islet cells. |
| 765 | 8746789 | Islets isolated from Sprague-Dawley rats were cultured with or without recombinant human IL-1 beta and TGF-beta. |
| 766 | 8746789 | Accumulated insulin secretion, cytokine-induced cytotoxicity, and islet cell expression of glutamic acid decarboxylase 65 (GAD-65) and heat-shock protein 70 (HSP-70) were measured in this study. |
| 767 | 8746789 | We found that (1) IL-1 beta at 50 and 100 pg/ml inhibited insulin secretion by 41.9 +/- 14.8 and 52.6 +/- 3.5% and induced cytotoxicity by 46.5 +/- 17.3 and 54.1 +/- 6.1%, respectively. |
| 768 | 8746789 | IL-1 beta at 1000 pg/ml significantly increased HSP-70 expression and decreased GAD-65 expression. (2) TGF-beta at 0.1, 1, 10, and 40 ng/ml had no significant effect on insulin secretion and did not induce cytotoxicity, TGF-beta at 40 ng/ml had no effect on the expression of either HSP-70 or GAD-65. (3) In combination, TGF-beta at 1, 10, and 40 ng/ml did not antagonize the IL-1 beta (50 and 100 pg/ml)-induced inhibition of insulin secretion or cytotoxicity; TGF-beta (40 ng/ml) did not block the effects of IL-1 beta (1000 pg/ml) on HSP-70 or GAD-65 expression. |
| 769 | 8746789 | In conclusion, recombinant human TGF-beta does not counteract these effects of recombinant human IL-1 beta on rat pancreatic islet cells. |
| 770 | 8746789 | Recombinant human transforming growth factor beta does not inhibit the effects of interleukin-1 beta on pancreatic islet cells. |
| 771 | 8746789 | The macrophage-derived cytokine, interleukin-1 beta (IL-1 beta), has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct cytotoxicity, and alteration of islet cell antigen expression. |
| 772 | 8746789 | Because transforming growth factor beta (TGF-beta) has been reported to inhibit IL-1 receptor expression in several lymphoid and progenitor cell lines, to induce IL-1 receptor antagonist protein (IRAP) production in human peripheral blood monocytes, and to antagonize several effects of inflammatory cytokines and because oral tolerance may be mediated in part by TGF-beta released by regulatory T lymphocytes, we investigated whether TGF-beta counteracted the effects of IL-1 beta on islet cells. |
| 773 | 8746789 | Islets isolated from Sprague-Dawley rats were cultured with or without recombinant human IL-1 beta and TGF-beta. |
| 774 | 8746789 | Accumulated insulin secretion, cytokine-induced cytotoxicity, and islet cell expression of glutamic acid decarboxylase 65 (GAD-65) and heat-shock protein 70 (HSP-70) were measured in this study. |
| 775 | 8746789 | We found that (1) IL-1 beta at 50 and 100 pg/ml inhibited insulin secretion by 41.9 +/- 14.8 and 52.6 +/- 3.5% and induced cytotoxicity by 46.5 +/- 17.3 and 54.1 +/- 6.1%, respectively. |
| 776 | 8746789 | IL-1 beta at 1000 pg/ml significantly increased HSP-70 expression and decreased GAD-65 expression. (2) TGF-beta at 0.1, 1, 10, and 40 ng/ml had no significant effect on insulin secretion and did not induce cytotoxicity, TGF-beta at 40 ng/ml had no effect on the expression of either HSP-70 or GAD-65. (3) In combination, TGF-beta at 1, 10, and 40 ng/ml did not antagonize the IL-1 beta (50 and 100 pg/ml)-induced inhibition of insulin secretion or cytotoxicity; TGF-beta (40 ng/ml) did not block the effects of IL-1 beta (1000 pg/ml) on HSP-70 or GAD-65 expression. |
| 777 | 8746789 | In conclusion, recombinant human TGF-beta does not counteract these effects of recombinant human IL-1 beta on rat pancreatic islet cells. |
| 778 | 8757636 | However, reverse-transcription PCR and ELISA measurements of cytokine mRNA and protein levels showed that the GAD65-reactive T cells from both line 5 and line 12 mice produced higher levels of IL-4 and lower levels of IFN-gamma than similar T cells from standard NOD/Lt mice. |
| 779 | 8760354 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in beta-cell destruction and immune regulation. |
| 780 | 8760354 | A major target of beta-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). |
| 781 | 8760354 | Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. |
| 782 | 8760354 | Incubation of islets with interleukin (IL)-1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24 h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. |
| 783 | 8760354 | Incubation of islets for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. |
| 784 | 8760354 | Inhibition of GAD65 and GAD67 protein synthesis by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). |
| 785 | 8760354 | Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1 beta and completely restored to baseline levels by NMMA. |
| 786 | 8760354 | Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the level of cytokine gene transcription. |
| 787 | 8760354 | As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of beta-cell destruction in IDDM. |
| 788 | 8760354 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in beta-cell destruction and immune regulation. |
| 789 | 8760354 | A major target of beta-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). |
| 790 | 8760354 | Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. |
| 791 | 8760354 | Incubation of islets with interleukin (IL)-1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24 h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. |
| 792 | 8760354 | Incubation of islets for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. |
| 793 | 8760354 | Inhibition of GAD65 and GAD67 protein synthesis by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). |
| 794 | 8760354 | Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1 beta and completely restored to baseline levels by NMMA. |
| 795 | 8760354 | Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the level of cytokine gene transcription. |
| 796 | 8760354 | As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of beta-cell destruction in IDDM. |
| 797 | 8760354 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in beta-cell destruction and immune regulation. |
| 798 | 8760354 | A major target of beta-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). |
| 799 | 8760354 | Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. |
| 800 | 8760354 | Incubation of islets with interleukin (IL)-1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24 h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. |
| 801 | 8760354 | Incubation of islets for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. |
| 802 | 8760354 | Inhibition of GAD65 and GAD67 protein synthesis by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). |
| 803 | 8760354 | Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1 beta and completely restored to baseline levels by NMMA. |
| 804 | 8760354 | Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the level of cytokine gene transcription. |
| 805 | 8760354 | As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of beta-cell destruction in IDDM. |
| 806 | 8760354 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in beta-cell destruction and immune regulation. |
| 807 | 8760354 | A major target of beta-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). |
| 808 | 8760354 | Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. |
| 809 | 8760354 | Incubation of islets with interleukin (IL)-1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24 h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. |
| 810 | 8760354 | Incubation of islets for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. |
| 811 | 8760354 | Inhibition of GAD65 and GAD67 protein synthesis by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). |
| 812 | 8760354 | Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1 beta and completely restored to baseline levels by NMMA. |
| 813 | 8760354 | Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the level of cytokine gene transcription. |
| 814 | 8760354 | As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of beta-cell destruction in IDDM. |
| 815 | 8760354 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in beta-cell destruction and immune regulation. |
| 816 | 8760354 | A major target of beta-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). |
| 817 | 8760354 | Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. |
| 818 | 8760354 | Incubation of islets with interleukin (IL)-1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24 h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. |
| 819 | 8760354 | Incubation of islets for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. |
| 820 | 8760354 | Inhibition of GAD65 and GAD67 protein synthesis by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). |
| 821 | 8760354 | Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1 beta and completely restored to baseline levels by NMMA. |
| 822 | 8760354 | Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the level of cytokine gene transcription. |
| 823 | 8760354 | As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of beta-cell destruction in IDDM. |
| 824 | 8781713 | Since glutamic acid decarboxylase-65 (GAD-65) is a target autoantigen in IDDM, we investigated whether the cytokines IL-1 beta, TNF alpha IFN gamma altered islet cell expression of GAD-65 and whether the effect of cytokines on GAD-65 expression was similar to their effect on insulin secretion. |
| 825 | 8781713 | We found that: 1) IL-1 beta at low dose (1 U/ml) which stimulated insulin secretion, had no effect on GAD-65 expression, whereas higher doses of IL-1 beta (10, 100, 1000 U/ml) which inhibited insulin secretion, decreased GAD-65 expression. 2) TNF alpha at doses of 10, 100, 1000 U/ml which stimulated insulin secretion had no effect on GAD-65 expression. 3) IFN gamma at doses of 10, 100, 1000 U/ml had no effect on insulin secretion or on GAD-65 expression. 4) In combination, IL-1 beta plus TNF alpha and IFN gamma showed a similar inhibitory effect on GAD-65 expression as IL-1 beta alone. |
| 826 | 8781713 | In summary: 1) IL-1 beta dramatically inhibits GAD-65 expression. 2) TNF alpha and IFN gamma have no effect on GAD-65 expression. |
| 827 | 8781713 | Of these three cytokines, IL-1 beta is the primary cytokine affecting GAD-65 expression. |
| 828 | 8781713 | Since glutamic acid decarboxylase-65 (GAD-65) is a target autoantigen in IDDM, we investigated whether the cytokines IL-1 beta, TNF alpha IFN gamma altered islet cell expression of GAD-65 and whether the effect of cytokines on GAD-65 expression was similar to their effect on insulin secretion. |
| 829 | 8781713 | We found that: 1) IL-1 beta at low dose (1 U/ml) which stimulated insulin secretion, had no effect on GAD-65 expression, whereas higher doses of IL-1 beta (10, 100, 1000 U/ml) which inhibited insulin secretion, decreased GAD-65 expression. 2) TNF alpha at doses of 10, 100, 1000 U/ml which stimulated insulin secretion had no effect on GAD-65 expression. 3) IFN gamma at doses of 10, 100, 1000 U/ml had no effect on insulin secretion or on GAD-65 expression. 4) In combination, IL-1 beta plus TNF alpha and IFN gamma showed a similar inhibitory effect on GAD-65 expression as IL-1 beta alone. |
| 830 | 8781713 | In summary: 1) IL-1 beta dramatically inhibits GAD-65 expression. 2) TNF alpha and IFN gamma have no effect on GAD-65 expression. |
| 831 | 8781713 | Of these three cytokines, IL-1 beta is the primary cytokine affecting GAD-65 expression. |
| 832 | 8781713 | Since glutamic acid decarboxylase-65 (GAD-65) is a target autoantigen in IDDM, we investigated whether the cytokines IL-1 beta, TNF alpha IFN gamma altered islet cell expression of GAD-65 and whether the effect of cytokines on GAD-65 expression was similar to their effect on insulin secretion. |
| 833 | 8781713 | We found that: 1) IL-1 beta at low dose (1 U/ml) which stimulated insulin secretion, had no effect on GAD-65 expression, whereas higher doses of IL-1 beta (10, 100, 1000 U/ml) which inhibited insulin secretion, decreased GAD-65 expression. 2) TNF alpha at doses of 10, 100, 1000 U/ml which stimulated insulin secretion had no effect on GAD-65 expression. 3) IFN gamma at doses of 10, 100, 1000 U/ml had no effect on insulin secretion or on GAD-65 expression. 4) In combination, IL-1 beta plus TNF alpha and IFN gamma showed a similar inhibitory effect on GAD-65 expression as IL-1 beta alone. |
| 834 | 8781713 | In summary: 1) IL-1 beta dramatically inhibits GAD-65 expression. 2) TNF alpha and IFN gamma have no effect on GAD-65 expression. |
| 835 | 8781713 | Of these three cytokines, IL-1 beta is the primary cytokine affecting GAD-65 expression. |
| 836 | 8781713 | Since glutamic acid decarboxylase-65 (GAD-65) is a target autoantigen in IDDM, we investigated whether the cytokines IL-1 beta, TNF alpha IFN gamma altered islet cell expression of GAD-65 and whether the effect of cytokines on GAD-65 expression was similar to their effect on insulin secretion. |
| 837 | 8781713 | We found that: 1) IL-1 beta at low dose (1 U/ml) which stimulated insulin secretion, had no effect on GAD-65 expression, whereas higher doses of IL-1 beta (10, 100, 1000 U/ml) which inhibited insulin secretion, decreased GAD-65 expression. 2) TNF alpha at doses of 10, 100, 1000 U/ml which stimulated insulin secretion had no effect on GAD-65 expression. 3) IFN gamma at doses of 10, 100, 1000 U/ml had no effect on insulin secretion or on GAD-65 expression. 4) In combination, IL-1 beta plus TNF alpha and IFN gamma showed a similar inhibitory effect on GAD-65 expression as IL-1 beta alone. |
| 838 | 8781713 | In summary: 1) IL-1 beta dramatically inhibits GAD-65 expression. 2) TNF alpha and IFN gamma have no effect on GAD-65 expression. |
| 839 | 8781713 | Of these three cytokines, IL-1 beta is the primary cytokine affecting GAD-65 expression. |
| 840 | 8816973 | The processes that lead to the production of islet cell autoantibodies in insulin-dependent (type 1) diabetes mellitus (IDDM) are largely unknown. |
| 841 | 8816973 | The high relative avidities for GAD65 of MICA 1, 3, 4 and 6 and their high, nonrandom ratio of replacement versus silent mutations in the antigen binding regions indicated that the humoral response to GAD65 is driven by the antigen. |
| 842 | 8816973 | The results suggest that, in humans, an antigen driven B cell activation and affinity maturation process may contribute to the production of GAD65-autoantibodies found in patients with IDDM. |
| 843 | 8816973 | The processes that lead to the production of islet cell autoantibodies in insulin-dependent (type 1) diabetes mellitus (IDDM) are largely unknown. |
| 844 | 8816973 | The high relative avidities for GAD65 of MICA 1, 3, 4 and 6 and their high, nonrandom ratio of replacement versus silent mutations in the antigen binding regions indicated that the humoral response to GAD65 is driven by the antigen. |
| 845 | 8816973 | The results suggest that, in humans, an antigen driven B cell activation and affinity maturation process may contribute to the production of GAD65-autoantibodies found in patients with IDDM. |
| 846 | 8816972 | Insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse results from a T lymphocyte mediated destruction of the insulin-producing beta cells of the pancreas and serves as a model for human type I diabetes. |
| 847 | 8816972 | It has previously been shown that a T helper 1 (Th1) response to the islet antigen, glutamic acid decarboxylase (GAD65, henceforth GAD) spontaneously develops in NOD mice concurrent with the onset of lymphocytic infiltration into the islets (insulitis). |
| 848 | 8816972 | Each hybridoma displayed a unique cytokine profile when stimulated with peptides 524-538 and 527-541, assaying IL-2, IFN-gamma, and IL-5 production by peptide-stimulated hybridomas. |
| 849 | 8816982 | We analysed the relation between humoral and cellular immunity to multiple islet cell antigens, including human insulin, glutamate decarboxylase GAD65, tyrosine phosphatase (ICA512/IA2), human pancreas and RIN cells in 28 patients with newly diagnosed type 1 diabetes and 9 antibody-positive (Ab+) relatives at high risk for type 1 diabetes. |
| 850 | 8816982 | Further-more, we found that T-cell reactivity to GAD was associated with T-cell reactivity to RIN cells, whereas reactivity to ICA512 and insulin was not associated with any other T-cell response. |
| 851 | 8816982 | Likewise, antibody response to ICA512/IA2 correlated with antibodies to human pancreas (ICA), whereas antibody response to GAD or insulin was not related to any other antibody response. |
| 852 | 8820987 | After fusion of splenocytes from a Balb/c mouse which received three injections of human recombinant GAD65 44 hybridomas producing monoclonal GAD antibodies (mc-GAD Ab) could be established. 35 out of the 44 mc-GAD Ab specifically recognized the GAD65 isoform, whereas 9 showed a cross-reactivity with GAD67. |
| 853 | 8824714 | Rat GAD65 was expressed as a fusion protein in the expression vector RSET and inhibited ICA (GAD+ICA) in 26% of 23 recent onset patients, 29% of 14 ICA positive first degree relatives (FDR) who progressed to diabetes (prediabetics) and 50% of 20 FDR who did not progress to diabetes 18 months to 5 years (31 +/- 14 months) after collection of the sample. |
| 854 | 8824714 | GAD+ICA were inversely associated with the presence of insulin autoantibodies (IAA) (P = 0.006). |
| 855 | 8824714 | GAD antibodies (GAD-Ab) were also detected by immunoprecipitation of in vitro transcribed and translated [35S] methionine-labelled human GAD65. |
| 856 | 8824714 | Rat GAD65 was expressed as a fusion protein in the expression vector RSET and inhibited ICA (GAD+ICA) in 26% of 23 recent onset patients, 29% of 14 ICA positive first degree relatives (FDR) who progressed to diabetes (prediabetics) and 50% of 20 FDR who did not progress to diabetes 18 months to 5 years (31 +/- 14 months) after collection of the sample. |
| 857 | 8824714 | GAD+ICA were inversely associated with the presence of insulin autoantibodies (IAA) (P = 0.006). |
| 858 | 8824714 | GAD antibodies (GAD-Ab) were also detected by immunoprecipitation of in vitro transcribed and translated [35S] methionine-labelled human GAD65. |
| 859 | 8845050 | Glutamic acid decarboxylase (GAD) has been shown to exist as two isoforms with molecular weights of 65 kD (GAD65) and 67 kD (GAD67) in the central nervous system as well as in several non-neuronal tissues, including the pancreatic islets. |
| 860 | 8845050 | Recently, this enzyme has been proposed as a key beta-cell autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 861 | 8845050 | In the adult pig, GAD65 was localized exclusively in most of the beta cells, whereas GAD67, in addition to being present in a majority of the beta cells, was also seen in a proportion of glucagon and somatostatin labelled cells. |
| 862 | 8845050 | The predominant expression of both the isoforms in porcine beta cells suggests that islet cells from this species may act as a suitable cellular model for study of GAD autoreactivity during the early stages of IDDM. |
| 863 | 8845050 | Glutamic acid decarboxylase (GAD) has been shown to exist as two isoforms with molecular weights of 65 kD (GAD65) and 67 kD (GAD67) in the central nervous system as well as in several non-neuronal tissues, including the pancreatic islets. |
| 864 | 8845050 | Recently, this enzyme has been proposed as a key beta-cell autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 865 | 8845050 | In the adult pig, GAD65 was localized exclusively in most of the beta cells, whereas GAD67, in addition to being present in a majority of the beta cells, was also seen in a proportion of glucagon and somatostatin labelled cells. |
| 866 | 8845050 | The predominant expression of both the isoforms in porcine beta cells suggests that islet cells from this species may act as a suitable cellular model for study of GAD autoreactivity during the early stages of IDDM. |
| 867 | 8864827 | Detection of autoantibodies to the pancreatic islet heat shock protein 60 in insulin-dependent diabetes mellitus. |
| 868 | 8864827 | We found no relationship between the levels of hsp60 antibodies and islet cell antibodies (ICA) or antibodies to glutamic acid decarboxylase (GAD65) in IDDM patients. |
| 869 | 8864827 | Although the positivity was low, the detection of hsp60 antibodies may be helpful for diagnosis of IDDM especially in GAD65 Ab- or JCA-negative Japanese patients. |
| 870 | 8864827 | Detection of autoantibodies to the pancreatic islet heat shock protein 60 in insulin-dependent diabetes mellitus. |
| 871 | 8864827 | We found no relationship between the levels of hsp60 antibodies and islet cell antibodies (ICA) or antibodies to glutamic acid decarboxylase (GAD65) in IDDM patients. |
| 872 | 8864827 | Although the positivity was low, the detection of hsp60 antibodies may be helpful for diagnosis of IDDM especially in GAD65 Ab- or JCA-negative Japanese patients. |
| 873 | 8877294 | Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM. |
| 874 | 8877294 | The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. |
| 875 | 8877294 | We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. |
| 876 | 8877294 | We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children. |
| 877 | 8877294 | Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM. |
| 878 | 8877294 | The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. |
| 879 | 8877294 | We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. |
| 880 | 8877294 | We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children. |
| 881 | 8877294 | Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM. |
| 882 | 8877294 | The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. |
| 883 | 8877294 | We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. |
| 884 | 8877294 | We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children. |
| 885 | 8877294 | Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM. |
| 886 | 8877294 | The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. |
| 887 | 8877294 | We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. |
| 888 | 8877294 | We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children. |
| 889 | 8904930 | To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. |
| 890 | 8904930 | Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. |
| 891 | 8904930 | The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. |
| 892 | 8904930 | In conclusion, our data show that even after common immunization of a nondiabetes-susceptible mouse strain, monoclonal were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4-17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the beta-cell destruction in type 1 diabetes mellitus. |
| 893 | 8904930 | To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. |
| 894 | 8904930 | Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. |
| 895 | 8904930 | The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. |
| 896 | 8904930 | In conclusion, our data show that even after common immunization of a nondiabetes-susceptible mouse strain, monoclonal were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4-17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the beta-cell destruction in type 1 diabetes mellitus. |
| 897 | 8904930 | To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. |
| 898 | 8904930 | Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. |
| 899 | 8904930 | The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. |
| 900 | 8904930 | In conclusion, our data show that even after common immunization of a nondiabetes-susceptible mouse strain, monoclonal were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4-17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the beta-cell destruction in type 1 diabetes mellitus. |
| 901 | 8904930 | To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. |
| 902 | 8904930 | Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. |
| 903 | 8904930 | The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. |
| 904 | 8904930 | In conclusion, our data show that even after common immunization of a nondiabetes-susceptible mouse strain, monoclonal were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4-17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the beta-cell destruction in type 1 diabetes mellitus. |
| 905 | 8932998 | Proliferative lymphocyte responses to virus antigens homologous to GAD65 in IDDM. |
| 906 | 8932998 | Virus infection has been proposed as an initiating factor in the aetiology of insulin-dependent diabetes mellitus (IDDM). |
| 907 | 8932998 | The frequency of positive response to the coxsackie B viruses was also significantly higher in IDDM subjects expressing the DRB 1*04 major histocompatibility complex (MHC) haplotype than the DRB 1*03 haplotype. |
| 908 | 8932998 | These results indicate a disease and MHC class II association between coxsackie B virus infection and IDDM and an association between adenovirus infection and IDDM. |
| 909 | 8933284 | IA-2 and IA-2 beta are major autoantigens in IDDM and the precursors of the 40 kDa and 37 kDa tryptic fragments. |
| 910 | 8933284 | Serological studies revealed that a high percentage of patients with IDDM have autoantibodies to IA-2/IA-2 beta and that the presence of these autoantibodies in otherwise normal individuals is highly predictive in identifying those at risk of ultimately developing clinical diabetes. |
| 911 | 8933284 | Moreover, many patients who are ICA positive, but who do not have Abs to GAD65, have Abs to IA-2/IA-2 beta. |
| 912 | 8933284 | It is concluded that IA-2/IA-2 beta are major autoantigens in IDDM and together with GAD65 are responsible for much of the reactivity of ICA with pancreatic islets. |
| 913 | 8933286 | Detection of glutamic acid decarboxylase (GAD) autoantibodies by indirect immunofluorescence using CHO cells expressing recombinant human GAD65. |
| 914 | 8933286 | The reaction between human glutamic acid decarboxylase (GAD65) expressed in CHO cells and GAD antibodies was studied by indirect immunofluorescence (IIF). |
| 915 | 8933286 | Twelve of 26 sera from newly-diagnosed insulin-dependent diabetes mellitus (IDDM) patients displayed a variety of anti GAD specific IIF images encompassing the two extremes observed with the monoclonal antibodies. |
| 916 | 8933286 | Our results established differences in anti GAD antibodies in terms of their capacity to recognize human GAD65 in the context of transformed CHO cells compared with conventional IP assays. |
| 917 | 8933286 | Detection of glutamic acid decarboxylase (GAD) autoantibodies by indirect immunofluorescence using CHO cells expressing recombinant human GAD65. |
| 918 | 8933286 | The reaction between human glutamic acid decarboxylase (GAD65) expressed in CHO cells and GAD antibodies was studied by indirect immunofluorescence (IIF). |
| 919 | 8933286 | Twelve of 26 sera from newly-diagnosed insulin-dependent diabetes mellitus (IDDM) patients displayed a variety of anti GAD specific IIF images encompassing the two extremes observed with the monoclonal antibodies. |
| 920 | 8933286 | Our results established differences in anti GAD antibodies in terms of their capacity to recognize human GAD65 in the context of transformed CHO cells compared with conventional IP assays. |
| 921 | 8933286 | Detection of glutamic acid decarboxylase (GAD) autoantibodies by indirect immunofluorescence using CHO cells expressing recombinant human GAD65. |
| 922 | 8933286 | The reaction between human glutamic acid decarboxylase (GAD65) expressed in CHO cells and GAD antibodies was studied by indirect immunofluorescence (IIF). |
| 923 | 8933286 | Twelve of 26 sera from newly-diagnosed insulin-dependent diabetes mellitus (IDDM) patients displayed a variety of anti GAD specific IIF images encompassing the two extremes observed with the monoclonal antibodies. |
| 924 | 8933286 | Our results established differences in anti GAD antibodies in terms of their capacity to recognize human GAD65 in the context of transformed CHO cells compared with conventional IP assays. |
| 925 | 8943434 | Autoreactive islet cell Abs (ICA) accompany the pathogenic destruction of pancreatic beta cells in insulin-dependent diabetes mellitus (IDDM). |
| 926 | 8943434 | We have isolated 4 new ICA-reactive B cell lines, one from a DR4/DR11-positive newly diagnosed IDDM patient (MICA 7) and three from a DR3 homozygous patient with both IDDM and Graves' disease (MICA 8-10). |
| 927 | 8943434 | Like MICA 1-6, MICA 7-10 are specific for GAD65, suggesting that GAD65-reactive B cells dominate the ICA response in IDDM. |
| 928 | 8943434 | MICA 1-6, 7, and 8-10, derived from three IDDM patients of different HLA haplotypes, define six different epitopes in GAD65 and represent tools to determine the spectrum, possible HLA association, and temporal order of epitope recognition in IDDM. |
| 929 | 8943434 | Autoreactive islet cell Abs (ICA) accompany the pathogenic destruction of pancreatic beta cells in insulin-dependent diabetes mellitus (IDDM). |
| 930 | 8943434 | We have isolated 4 new ICA-reactive B cell lines, one from a DR4/DR11-positive newly diagnosed IDDM patient (MICA 7) and three from a DR3 homozygous patient with both IDDM and Graves' disease (MICA 8-10). |
| 931 | 8943434 | Like MICA 1-6, MICA 7-10 are specific for GAD65, suggesting that GAD65-reactive B cells dominate the ICA response in IDDM. |
| 932 | 8943434 | MICA 1-6, 7, and 8-10, derived from three IDDM patients of different HLA haplotypes, define six different epitopes in GAD65 and represent tools to determine the spectrum, possible HLA association, and temporal order of epitope recognition in IDDM. |
| 933 | 8954025 | We analyzed sequential serum samples from 155 siblings and offspring (aged < 7 yr) of patients with type I diabetes from the Denver Diabetes Autoimmunity Study in the Young study and from a separate group of first degree relatives (aged 2-40 yr) for autoantibodies reacting with three defined autoantigens: glutamic acid decarboxylase (GAD65), insulin, and ICA512/IA-2. |
| 934 | 8969635 | We evaluated a new, commercially developed radioimmunoprecipitation assay for measuring glutamic acid decarboxylase (GAD) antibodies by using recombinant human GAD65. |
| 935 | 8969635 | We found GAD antibodies in 74% (23 of 31; 95% confidence interval 55-88%), 70% (14 of 20; 46-88%), and 65% (28 of 43; 49-79%) of patients at, respectively, < or = 1 year, 1-2 years, and 2-4 years after the onset of insulin-dependent diabetes mellitus (IDDM) and in 30% (30 of 99; 21-40%) of patients with long-term diabetes (4-22 years). |
| 936 | 8969635 | We also detected GAD antibodies in 8% (9 of 106; 4-16%) of patients with non-insulin-dependent diabetes mellitus (NIDDM). |
| 937 | 8969635 | The frequency of GAD antibodies in the NIDDM group was markedly higher in the insulin-deficient patients [67% (6 of 9; 30-93%)], who initially were nonketotic and non-insulin-dependent for > or = 6 months but later became insulin dependent, than in the non-insulin-deficient patients [3% (3 of 97; 1-9%)]. |
| 938 | 8969635 | This new commercial assay is easy to use and provides a specific and sensitive method for evaluating GAD antibodies in IDDM. |
| 939 | 8989249 | The aim of the present study was to investigate the presence of anti-AADC antibodies in a large cohort of patients with APS I, and in patients with isolated insulin-dependent diabetes mellitus (IDDM). |
| 940 | 8989249 | We found autoantibodies against AADC in 35 of 69 patients (51%) with APS I but in none of 138 patients with isolated IDDM or 91 healthy controls. |
| 941 | 8989249 | Of the 9 APS I patients with IDDM, 5 had antibodies against both AADC and glutamate decarboxylase, 2 against AADC only, and 2 against glutamate decarboxylase only. |
| 942 | 8989249 | Thus, an autoimmune reactivity against AADC may be involved in the pathogenesis of autoimmune chronic active hepatitis and vitiligo in APS I patients, whereas the role of AADC in the development of IDDM in these patients remains to be determined. |
| 943 | 9028724 | IA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients and help predict impending diabetes in their siblings. |
| 944 | 9028724 | IA-2 has been identified as an autoantigen that is recognized by immunoglobulins from insulin-dependent diabetic (IDDM) patients. |
| 945 | 9028724 | Using a liquid phase radiobinding assay, we performed an IA-2-autoantibody (IA-2-Ab) assay in 474 IDDM patients and 482 non-diabetic control subjects aged 0-3 years. |
| 946 | 9028724 | IA-2-Ab levels were positively correlated with ICA titres (p < 0.001) and HLA DQ A1*0301-DQ B1*0.02 (p < 0.003) by multivariate analysis. |
| 947 | 9028724 | In a group of 481 non-diabetic siblings (age 0-39 years) of IDDM patients only 7 were IA-2-Ab positive (1.5%). |
| 948 | 9028724 | In conclusion, IA-2-Ab show a high diagnostic specificity for IDDM and are predictive markers of impending diabetes in siblings of patients. |
| 949 | 9048916 | Reliable genetic and immunological markers are important in the prediction of insulin-dependent diabetes mellitus (IDDM). |
| 950 | 9048916 | Since glutamic acid decarboxylase (GAD) is a candidate primary autoantigen, we examined the possible linkage between IDDM and the genes encoding GAD65 (GAD2, 10p11-12) and GAD67 (GAD1, 2q31) in 58 Danish IDDM affected sib pairs. |
| 951 | 9048916 | No evidence of linkage was found between IDDM and either of the genes encoding GAD. |
| 952 | 9048916 | Considering the high prevalence of GAD autoantibodies in IDDM, a putative genetic association between GAD and IDDM would be expected to affect most diabetic individuals. |
| 953 | 9048916 | Therefore, our data indicate that the association between GAD and IDDM is not genetically determined, and that microsatellites used in this study do not contribute to the prediction of IDDM. |
| 954 | 9058186 | Detection of serum autoantibodies to glutamic acid decarboxylase (GAD) is a new method to differentiate insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). |
| 955 | 9058186 | We also established a sandwich ELISA for anti-GAD Ab of the IgG class using GAD65 for coating and the anti-human IgG for detection and examined 54 sera of the IDDM patients and 45 sera of normal individuals. |
| 956 | 9073547 | Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. |
| 957 | 9073547 | Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. |
| 958 | 9073547 | We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. |
| 959 | 9073547 | In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. |
| 960 | 9073547 | We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. |
| 961 | 9073547 | We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. |
| 962 | 9073547 | When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. |
| 963 | 9073547 | Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. |
| 964 | 9073547 | In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. |
| 965 | 9073547 | Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM. |
| 966 | 9073547 | Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. |
| 967 | 9073547 | Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. |
| 968 | 9073547 | We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. |
| 969 | 9073547 | In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. |
| 970 | 9073547 | We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. |
| 971 | 9073547 | We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. |
| 972 | 9073547 | When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. |
| 973 | 9073547 | Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. |
| 974 | 9073547 | In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. |
| 975 | 9073547 | Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM. |
| 976 | 9073547 | Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. |
| 977 | 9073547 | Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. |
| 978 | 9073547 | We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. |
| 979 | 9073547 | In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. |
| 980 | 9073547 | We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. |
| 981 | 9073547 | We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. |
| 982 | 9073547 | When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. |
| 983 | 9073547 | Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. |
| 984 | 9073547 | In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. |
| 985 | 9073547 | Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM. |
| 986 | 9073547 | Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. |
| 987 | 9073547 | Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. |
| 988 | 9073547 | We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. |
| 989 | 9073547 | In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. |
| 990 | 9073547 | We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. |
| 991 | 9073547 | We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. |
| 992 | 9073547 | When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. |
| 993 | 9073547 | Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. |
| 994 | 9073547 | In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. |
| 995 | 9073547 | Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM. |
| 996 | 9073547 | Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. |
| 997 | 9073547 | Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. |
| 998 | 9073547 | We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. |
| 999 | 9073547 | In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. |
| 1000 | 9073547 | We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. |
| 1001 | 9073547 | We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. |
| 1002 | 9073547 | When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. |
| 1003 | 9073547 | Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. |
| 1004 | 9073547 | In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. |
| 1005 | 9073547 | Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM. |
| 1006 | 9073547 | Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. |
| 1007 | 9073547 | Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. |
| 1008 | 9073547 | We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. |
| 1009 | 9073547 | In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. |
| 1010 | 9073547 | We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. |
| 1011 | 9073547 | We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. |
| 1012 | 9073547 | When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. |
| 1013 | 9073547 | Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. |
| 1014 | 9073547 | In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. |
| 1015 | 9073547 | Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM. |
| 1016 | 9075795 | Combined analysis and single-step detection of GAD65 and IA2 autoantibodies in IDDM can replace the histochemical islet cell antibody test. |
| 1017 | 9075797 | To study the possible link between the gut immune system and IDDM, we tested the expression of the alpha4beta7-integrin, a homing receptor for MAdCAM-1, on GAD65-reactive lymphocytes. |
| 1018 | 9084973 | GAD65 is one of the major autoantigens associated with insulin-dependent diabetes mellitus (IDDM). |
| 1019 | 9084973 | The two peptides p17 and p18 of GAD65 that share sequence similarity with coxsackie virus (amino acid sequence identity: PEVKEK) appeared to be the major determinants of GAD65 recognized preferably by T cells from new-onset IDDM patients and their first degree relatives. |
| 1020 | 9084973 | In contrast, in our study unrelated control subjects frequently recognized the two GAD peptides (55%, 16/29), similar to first degree relatives (41%, 12/29) and IDDM patients post-onset (68%, 15/22). |
| 1021 | 9084973 | Moreover, this study demonstrated a positive correlation of T-cell proliferation to GAD p17 (amino acid 247-266) and p18 (amino acid 260-279) with simultaneous responses to both peptides in 13% of all subjects tested (n = 97) (p < 0.001). |
| 1022 | 9084973 | T-cell proliferation to GAD p17 was higher than to p18 in recent-onset diabetic patients, first degree relatives and unrelated control subjects (p < 0.02, p < 0.004, p < 0.002, respectively). |
| 1023 | 9099922 | Antibodies against this epitope were induced during enterovirus (including CBV) infections in initially healthy children who later progressed to clinical insulin-dependent diabetes mellitus (IDDM). |
| 1024 | 9099922 | Antibody responses were frequent also in constantly GAD65 antibody-negative non-diabetic children, and antibody levels did not differ between newly diagnosed IDDM patients and matched control subjects. |
| 1025 | 9112029 | Prevalence of GAD65 and IA-2 autoantibodies in IDDM patients affected by diabetic nephropathy. |
| 1026 | 9153283 | Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in insulin-dependent diabetes mellitus (IDDM). |
| 1027 | 9153283 | To identify the molecular ligands triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte lines was generated from peripheral blood of three recent onset IDDM patients. |
| 1028 | 9153283 | Our data reveal that (a) the T cell response to GAD65 is quite heterogenous in recent onset IDDM patients; (b) HLA-DR, not DQ, seems to be the principal restriction element used by T cells present at the onset of the disease; and (c) T cells responding to epitopes containing identical sequences to Coxsackie virus P2-C protein were not detected. |
| 1029 | 9153283 | Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in insulin-dependent diabetes mellitus (IDDM). |
| 1030 | 9153283 | To identify the molecular ligands triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte lines was generated from peripheral blood of three recent onset IDDM patients. |
| 1031 | 9153283 | Our data reveal that (a) the T cell response to GAD65 is quite heterogenous in recent onset IDDM patients; (b) HLA-DR, not DQ, seems to be the principal restriction element used by T cells present at the onset of the disease; and (c) T cells responding to epitopes containing identical sequences to Coxsackie virus P2-C protein were not detected. |
| 1032 | 9179463 | Combined measurements of GAD65 and ICA512 antibodies in acute onset and slowly progressive IDDM. |
| 1033 | 9179463 | Autoantibodies to 65 kD glutamic acid decarboxylase (GADAA) and ICA512 (ICA512AA) were measured by radioimmunoassays using as antigens in vitro transcribed and translated [35S]-methionine-labeled human GAD65 and ICA512 (IA-2). |
| 1034 | 9179463 | ICA512 radioassay, in combination with GAD assay may provide a useful diagnostic marker for IDDM especially in youth. |
| 1035 | 9179463 | Combined measurements of GAD65 and ICA512 antibodies in acute onset and slowly progressive IDDM. |
| 1036 | 9179463 | Autoantibodies to 65 kD glutamic acid decarboxylase (GADAA) and ICA512 (ICA512AA) were measured by radioimmunoassays using as antigens in vitro transcribed and translated [35S]-methionine-labeled human GAD65 and ICA512 (IA-2). |
| 1037 | 9179463 | ICA512 radioassay, in combination with GAD assay may provide a useful diagnostic marker for IDDM especially in youth. |
| 1038 | 9208924 | Autoantibodies to the islet-cell 65-kDa variant of glutamate decarboxylase (GAD65) are found in most insulin-dependent diabetes mellitus (IDDM) patients many years before the appearance of clinical symptoms of the disease. |
| 1039 | 9220540 | Autoantigens in insulin-dependent diabetes mellitus: molecular cloning and characterization of human IA-2 beta. |
| 1040 | 9220540 | Using recombinant human IA-2 beta, we developed a radioimmunoprecipitation assay to measure autoantibodies in the sera of patients with insulin-dependent diabetes mellitus (IDDM). |
| 1041 | 9220540 | Thirty-seven percent (28 of 76) of the IDDM sera-but less than 1% of the control sera (1 of 174)-reacted with IA-2 beta. |
| 1042 | 9220540 | The same IDDM sera tested for autoantibodies to IA-2 and glutamic acid decarboxylase (GAD65) showed that 64% (49 of 76) and 57% (43 of 76), respectively, were positive. |
| 1043 | 9220540 | Combination of any two markers, such as IA-2 beta and IA-2, or IA-2 beta and GAD65, or IA-2 and GAD65, revealed that 67%, 74%, and 87% of IDDM sera were positive for autoantibodies, respectively. |
| 1044 | 9220540 | Blocking of IDDM sera with recombinant IA-2, IA-2 beta, or GAD65 resulted in marked inhibition of reactivity of IDDM sera with pancreatic islet sections as measured by islet cell autoantibody immunofluorescence. |
| 1045 | 9220540 | Autoantigens in insulin-dependent diabetes mellitus: molecular cloning and characterization of human IA-2 beta. |
| 1046 | 9220540 | Using recombinant human IA-2 beta, we developed a radioimmunoprecipitation assay to measure autoantibodies in the sera of patients with insulin-dependent diabetes mellitus (IDDM). |
| 1047 | 9220540 | Thirty-seven percent (28 of 76) of the IDDM sera-but less than 1% of the control sera (1 of 174)-reacted with IA-2 beta. |
| 1048 | 9220540 | The same IDDM sera tested for autoantibodies to IA-2 and glutamic acid decarboxylase (GAD65) showed that 64% (49 of 76) and 57% (43 of 76), respectively, were positive. |
| 1049 | 9220540 | Combination of any two markers, such as IA-2 beta and IA-2, or IA-2 beta and GAD65, or IA-2 and GAD65, revealed that 67%, 74%, and 87% of IDDM sera were positive for autoantibodies, respectively. |
| 1050 | 9220540 | Blocking of IDDM sera with recombinant IA-2, IA-2 beta, or GAD65 resulted in marked inhibition of reactivity of IDDM sera with pancreatic islet sections as measured by islet cell autoantibody immunofluorescence. |
| 1051 | 9220540 | Autoantigens in insulin-dependent diabetes mellitus: molecular cloning and characterization of human IA-2 beta. |
| 1052 | 9220540 | Using recombinant human IA-2 beta, we developed a radioimmunoprecipitation assay to measure autoantibodies in the sera of patients with insulin-dependent diabetes mellitus (IDDM). |
| 1053 | 9220540 | Thirty-seven percent (28 of 76) of the IDDM sera-but less than 1% of the control sera (1 of 174)-reacted with IA-2 beta. |
| 1054 | 9220540 | The same IDDM sera tested for autoantibodies to IA-2 and glutamic acid decarboxylase (GAD65) showed that 64% (49 of 76) and 57% (43 of 76), respectively, were positive. |
| 1055 | 9220540 | Combination of any two markers, such as IA-2 beta and IA-2, or IA-2 beta and GAD65, or IA-2 and GAD65, revealed that 67%, 74%, and 87% of IDDM sera were positive for autoantibodies, respectively. |
| 1056 | 9220540 | Blocking of IDDM sera with recombinant IA-2, IA-2 beta, or GAD65 resulted in marked inhibition of reactivity of IDDM sera with pancreatic islet sections as measured by islet cell autoantibody immunofluorescence. |
| 1057 | 9223318 | Glutamic acid decarboxylase isoform 2 (GAD65; EC 4.1.1.15) has been identified as a key target autoantigen of insulin-dependent diabetes mellitus (IDDM). |
| 1058 | 9223318 | IDDM is genetically associated with the major histocompatibility complex (MHC), and particular alleles from the HLA-DQ and HLA-DR loci contribute to disease. |
| 1059 | 9223318 | We have utilized HLA-DR(alpha1*0101,beta1*0401) (hereafter referred to as DR0401), human CD4, murine class II null triple transgenic mice and recombinant GAD65 to generate T cell hybridomas, and we have used overlapping sets of peptides to map the immunodominant epitopes of this autoantigen. |
| 1060 | 9223318 | Immunodominant GAD65 epitopes defined in transgenic mice correspond to GAD65 regions previously shown to elicit T cell responses specifically in DR0401 IDDM patients, underscoring the validity of this approach. |
| 1061 | 9223318 | Glutamic acid decarboxylase isoform 2 (GAD65; EC 4.1.1.15) has been identified as a key target autoantigen of insulin-dependent diabetes mellitus (IDDM). |
| 1062 | 9223318 | IDDM is genetically associated with the major histocompatibility complex (MHC), and particular alleles from the HLA-DQ and HLA-DR loci contribute to disease. |
| 1063 | 9223318 | We have utilized HLA-DR(alpha1*0101,beta1*0401) (hereafter referred to as DR0401), human CD4, murine class II null triple transgenic mice and recombinant GAD65 to generate T cell hybridomas, and we have used overlapping sets of peptides to map the immunodominant epitopes of this autoantigen. |
| 1064 | 9223318 | Immunodominant GAD65 epitopes defined in transgenic mice correspond to GAD65 regions previously shown to elicit T cell responses specifically in DR0401 IDDM patients, underscoring the validity of this approach. |
| 1065 | 9223318 | Glutamic acid decarboxylase isoform 2 (GAD65; EC 4.1.1.15) has been identified as a key target autoantigen of insulin-dependent diabetes mellitus (IDDM). |
| 1066 | 9223318 | IDDM is genetically associated with the major histocompatibility complex (MHC), and particular alleles from the HLA-DQ and HLA-DR loci contribute to disease. |
| 1067 | 9223318 | We have utilized HLA-DR(alpha1*0101,beta1*0401) (hereafter referred to as DR0401), human CD4, murine class II null triple transgenic mice and recombinant GAD65 to generate T cell hybridomas, and we have used overlapping sets of peptides to map the immunodominant epitopes of this autoantigen. |
| 1068 | 9223318 | Immunodominant GAD65 epitopes defined in transgenic mice correspond to GAD65 regions previously shown to elicit T cell responses specifically in DR0401 IDDM patients, underscoring the validity of this approach. |
| 1069 | 9231650 | Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. |
| 1070 | 9231650 | To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2, IA-2ic, glutamic acid decarboxylase (GAD65), and islet cell antibodies (ICAs) in 1) 60 newly diagnosed type 1 diabetic patients followed for 1 year, 2) 31 monozygotic twin pairs discordant for type 1 diabetes followed up to 12 years (11 twins developed diabetes), 3) 18 dizygotic twin pairs discordant for type 1 diabetes, and 4) normal healthy control subjects. |
| 1071 | 9231650 | Newly diagnosed type 1 diabetic patients frequently had antibodies to IA-2 (62%), IA-2ic (67%), GAD65 (77%), and ICAs (85%). |
| 1072 | 9231650 | In summary, IA-2 emerges as a major antigen associated with type 1 diabetes and distinct from GAD65. |
| 1073 | 9231650 | Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. |
| 1074 | 9231650 | To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2, IA-2ic, glutamic acid decarboxylase (GAD65), and islet cell antibodies (ICAs) in 1) 60 newly diagnosed type 1 diabetic patients followed for 1 year, 2) 31 monozygotic twin pairs discordant for type 1 diabetes followed up to 12 years (11 twins developed diabetes), 3) 18 dizygotic twin pairs discordant for type 1 diabetes, and 4) normal healthy control subjects. |
| 1075 | 9231650 | Newly diagnosed type 1 diabetic patients frequently had antibodies to IA-2 (62%), IA-2ic (67%), GAD65 (77%), and ICAs (85%). |
| 1076 | 9231650 | In summary, IA-2 emerges as a major antigen associated with type 1 diabetes and distinct from GAD65. |
| 1077 | 9231650 | Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. |
| 1078 | 9231650 | To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2, IA-2ic, glutamic acid decarboxylase (GAD65), and islet cell antibodies (ICAs) in 1) 60 newly diagnosed type 1 diabetic patients followed for 1 year, 2) 31 monozygotic twin pairs discordant for type 1 diabetes followed up to 12 years (11 twins developed diabetes), 3) 18 dizygotic twin pairs discordant for type 1 diabetes, and 4) normal healthy control subjects. |
| 1079 | 9231650 | Newly diagnosed type 1 diabetic patients frequently had antibodies to IA-2 (62%), IA-2ic (67%), GAD65 (77%), and ICAs (85%). |
| 1080 | 9231650 | In summary, IA-2 emerges as a major antigen associated with type 1 diabetes and distinct from GAD65. |
| 1081 | 9237801 | Polymorphism of the genes coding for the human histocompatibility leukocyte antigen class II DR and DQ molecules makes the single largest genetic contribution to the risk of developing insulin-dependent diabetes mellitus (IDDM) and can be associated with highly elevated as well as decreased disease frequency. |
| 1082 | 9237801 | We have generated T cell lines (TCL) with specificity for the IDDM autoantigen 65 kDa glutamic acid decarboxylase (GAD65) from lymphocytes of two patients carrying HLA class II alleles associated with distinct risk of IDDM (DRB1*0101/0401 and 1302/1501). |
| 1083 | 9237801 | This epitope overlaps with a central GAD peptide binding to the high risk allele DQB1*0302 and containing a Coxsackie P2C-identical mimicry sequence, raising the possibility of competition of DRB5*0101 and DQB1*0302 for binding of a central GAD65 fragment. |
| 1084 | 9237801 | Polymorphism of the genes coding for the human histocompatibility leukocyte antigen class II DR and DQ molecules makes the single largest genetic contribution to the risk of developing insulin-dependent diabetes mellitus (IDDM) and can be associated with highly elevated as well as decreased disease frequency. |
| 1085 | 9237801 | We have generated T cell lines (TCL) with specificity for the IDDM autoantigen 65 kDa glutamic acid decarboxylase (GAD65) from lymphocytes of two patients carrying HLA class II alleles associated with distinct risk of IDDM (DRB1*0101/0401 and 1302/1501). |
| 1086 | 9237801 | This epitope overlaps with a central GAD peptide binding to the high risk allele DQB1*0302 and containing a Coxsackie P2C-identical mimicry sequence, raising the possibility of competition of DRB5*0101 and DQB1*0302 for binding of a central GAD65 fragment. |
| 1087 | 9243099 | Lyp controls the number of peripheral lymphocytes by reducing T cells of the RT6+ phenotype by almost 90%. |
| 1088 | 9243099 | The frequency of IFN gamma and interleukin (IL)-10 mRNA expressing cells in isolated thymocytes determined by quantitative image analysis, demonstrated an increased IFN gamma: IL-10 ratio in thymocytes from lyp/lyp homozygotes compared to lyp/+ and +/+ rats. |
| 1089 | 9243099 | Recombinant human glutamic acid decarboxylase (GAD65) increased the number of IFN gamma and IL-10 mRNA expressing thymocytes after in vitro culture. |
| 1090 | 9253351 | Antibodies to glutamic acid decarboxylase-65 (GAD65) are present in a number of autoimmune disorders, such as insulin-dependent (type 1) diabetes mellitus (IDDM), stiff man syndrome, and polyendocrine autoimmune disease. |
| 1091 | 9253351 | Antibodies to GAD in IDDM patients usually recognize conformation-dependent regions on GAD65 and rarely bind to the second isoform, glutamic acid decarboxylase-67 (GAD67). |
| 1092 | 9253351 | Using chimeric GAD proteins, we have shown that b35 targets the IDDM-E1 region of GAD65 (amino acids 240-435) whereas both b78 and b96 target the IDDM-E2 region of GAD65 (amino acids 451-570). |
| 1093 | 9253351 | Our results indicate that antibodies to GAD65 present in nondiabetic patients with multiple autoantibodies to endocrine organs show similarities to those in IDDM (by targeting IDDM-E1 and IDDM-E2 regions of GAD65) as well as subtle differences in epitope recognition (such as binding to denatured and reduced GAD65 and by protein footprinting). |
| 1094 | 9253351 | Antibodies to glutamic acid decarboxylase-65 (GAD65) are present in a number of autoimmune disorders, such as insulin-dependent (type 1) diabetes mellitus (IDDM), stiff man syndrome, and polyendocrine autoimmune disease. |
| 1095 | 9253351 | Antibodies to GAD in IDDM patients usually recognize conformation-dependent regions on GAD65 and rarely bind to the second isoform, glutamic acid decarboxylase-67 (GAD67). |
| 1096 | 9253351 | Using chimeric GAD proteins, we have shown that b35 targets the IDDM-E1 region of GAD65 (amino acids 240-435) whereas both b78 and b96 target the IDDM-E2 region of GAD65 (amino acids 451-570). |
| 1097 | 9253351 | Our results indicate that antibodies to GAD65 present in nondiabetic patients with multiple autoantibodies to endocrine organs show similarities to those in IDDM (by targeting IDDM-E1 and IDDM-E2 regions of GAD65) as well as subtle differences in epitope recognition (such as binding to denatured and reduced GAD65 and by protein footprinting). |
| 1098 | 9253351 | Antibodies to glutamic acid decarboxylase-65 (GAD65) are present in a number of autoimmune disorders, such as insulin-dependent (type 1) diabetes mellitus (IDDM), stiff man syndrome, and polyendocrine autoimmune disease. |
| 1099 | 9253351 | Antibodies to GAD in IDDM patients usually recognize conformation-dependent regions on GAD65 and rarely bind to the second isoform, glutamic acid decarboxylase-67 (GAD67). |
| 1100 | 9253351 | Using chimeric GAD proteins, we have shown that b35 targets the IDDM-E1 region of GAD65 (amino acids 240-435) whereas both b78 and b96 target the IDDM-E2 region of GAD65 (amino acids 451-570). |
| 1101 | 9253351 | Our results indicate that antibodies to GAD65 present in nondiabetic patients with multiple autoantibodies to endocrine organs show similarities to those in IDDM (by targeting IDDM-E1 and IDDM-E2 regions of GAD65) as well as subtle differences in epitope recognition (such as binding to denatured and reduced GAD65 and by protein footprinting). |
| 1102 | 9253351 | Antibodies to glutamic acid decarboxylase-65 (GAD65) are present in a number of autoimmune disorders, such as insulin-dependent (type 1) diabetes mellitus (IDDM), stiff man syndrome, and polyendocrine autoimmune disease. |
| 1103 | 9253351 | Antibodies to GAD in IDDM patients usually recognize conformation-dependent regions on GAD65 and rarely bind to the second isoform, glutamic acid decarboxylase-67 (GAD67). |
| 1104 | 9253351 | Using chimeric GAD proteins, we have shown that b35 targets the IDDM-E1 region of GAD65 (amino acids 240-435) whereas both b78 and b96 target the IDDM-E2 region of GAD65 (amino acids 451-570). |
| 1105 | 9253351 | Our results indicate that antibodies to GAD65 present in nondiabetic patients with multiple autoantibodies to endocrine organs show similarities to those in IDDM (by targeting IDDM-E1 and IDDM-E2 regions of GAD65) as well as subtle differences in epitope recognition (such as binding to denatured and reduced GAD65 and by protein footprinting). |
| 1106 | 9260198 | GAD65 is targeted by different patterns of autoantibodies [glutamic acid decarboxylase (GAD)-AAbs] in insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS). |
| 1107 | 9260198 | This fixation procedure was used to compare the immunoreactivity of GAD-AAb+ or GAD-AAb- islet cell cytoplasmic antibody-positive (ICA+) sera of IDDM (n = 27) and SMS patients (n = 3). |
| 1108 | 9260198 | The three SMS sera were reactive with GAD on fixed islets but showed a reduced titer, whereas the majority of IDDM sera (22/27; 81.5%) were not detectable; 70.6% (12/ 17) of GAD-AAb+ IDDM sera were not detectable on fixed islets. |
| 1109 | 9272278 | The lack of protection against diabetes following GAD65 treatment could hypothetically be explained by no or by an aberrant expression of GAD in BB-rat islet cells. |
| 1110 | 9300229 | High prevalence of GAD65 (and IA-2) antibodies in Japanese IDDM patients by a new immunoprecipitation assay based on recombinant human GAD65. |
| 1111 | 9300229 | Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. |
| 1112 | 9300229 | High prevalence of GAD65 (and IA-2) antibodies in Japanese IDDM patients by a new immunoprecipitation assay based on recombinant human GAD65. |
| 1113 | 9300229 | Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. |
| 1114 | 9344328 | Antibodies to the 40 kD antigen (identified as tyrosine phosphatase IA-2) and glutamate decarboxylase (GAD65) are strongly associated with insulin dependent diabetes mellitus (IDDM). |
| 1115 | 9358337 | We describe a sandwich ELISA based on monoclonal GAD65 antibodies (Mc-GAD65-Ab) of different epitope specificities to quantify GAD65 in pancreatic islets and in different organ/cell extracts and during the preparation of GAD from brain extracts. |
| 1116 | 9358337 | The detection limit was estimated to be 0.03 ng GAD65/ml using alkaline phosphatase (AP)-conjugated streptavidin. |
| 1117 | 9358337 | We describe a sandwich ELISA based on monoclonal GAD65 antibodies (Mc-GAD65-Ab) of different epitope specificities to quantify GAD65 in pancreatic islets and in different organ/cell extracts and during the preparation of GAD from brain extracts. |
| 1118 | 9358337 | The detection limit was estimated to be 0.03 ng GAD65/ml using alkaline phosphatase (AP)-conjugated streptavidin. |
| 1119 | 9368643 | Highly-sensitive and specific enzyme-linked immunosorbent assays for GAD65 autoantibodies using a thioredoxin-GAD65 fusion antigen. |
| 1120 | 9368643 | Autoantibodies against glutamic acid decarboxylase (GAD65) are present in the sera of most patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM). |
| 1121 | 9368643 | To detect GAD65 autoantibodies (GADA), we developed new enzyme-linked immunosorbent assays (ELISA) with a fusion protein thioredoxin-GAD65 (Trx-GAD65) produced in E. coli as the antigen. |
| 1122 | 9368643 | Highly-sensitive and specific enzyme-linked immunosorbent assays for GAD65 autoantibodies using a thioredoxin-GAD65 fusion antigen. |
| 1123 | 9368643 | Autoantibodies against glutamic acid decarboxylase (GAD65) are present in the sera of most patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM). |
| 1124 | 9368643 | To detect GAD65 autoantibodies (GADA), we developed new enzyme-linked immunosorbent assays (ELISA) with a fusion protein thioredoxin-GAD65 (Trx-GAD65) produced in E. coli as the antigen. |
| 1125 | 9368643 | Highly-sensitive and specific enzyme-linked immunosorbent assays for GAD65 autoantibodies using a thioredoxin-GAD65 fusion antigen. |
| 1126 | 9368643 | Autoantibodies against glutamic acid decarboxylase (GAD65) are present in the sera of most patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM). |
| 1127 | 9368643 | To detect GAD65 autoantibodies (GADA), we developed new enzyme-linked immunosorbent assays (ELISA) with a fusion protein thioredoxin-GAD65 (Trx-GAD65) produced in E. coli as the antigen. |
| 1128 | 9392483 | Quite unexpectedly, two GAD65-derived peptides near the COOH-terminus (p34 and p35) accelerated diabetes onset. |
| 1129 | 9392483 | Protection mediated by intrathymic administration with either intact islet cells or GAD65 were correlated with an upregulation of mRNA for T-helper 2 (Th2)-associated cytokines (interleukin [IL]-4, IL-10), concomitant with downregulation of Th1-associated interferon (IFN) transcripts (all normalized to T-cell receptor Cbeta transcripts) in islet-infiltrating lymphocytes. |
| 1130 | 9392483 | Protection mediated by the intrathymic administration of insulin B chain, however, correlated only with a modest upregulation of IL-4 and IL-10 transcript levels, and no diminution in IFN-gamma transcripts. |
| 1131 | 9392483 | In contrast, the diabetes-accelerating GAD65 p34 and p35 peptides were not associated with an immune deviation, expressing levels of IFN-gamma characteristic of islet-infiltrating lymphocytes in vehicle-injected NOD controls. |
| 1132 | 9421467 | GAD-reactive CD4+ Th1 cells induce diabetes in NOD/SCID mice. |
| 1133 | 9421467 | Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. |
| 1134 | 9421467 | Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4+ T cell line, designated 5A, that expresses TCRs encoding Vbeta2 and Vbeta12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524-543. |
| 1135 | 9421467 | After antigen-specific stimulation, 5A T cells secrete IFNgamma and TNFalpha/beta, but not IL-4. |
| 1136 | 9421467 | We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. |
| 1137 | 9421467 | Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM. |
| 1138 | 9421467 | GAD-reactive CD4+ Th1 cells induce diabetes in NOD/SCID mice. |
| 1139 | 9421467 | Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. |
| 1140 | 9421467 | Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4+ T cell line, designated 5A, that expresses TCRs encoding Vbeta2 and Vbeta12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524-543. |
| 1141 | 9421467 | After antigen-specific stimulation, 5A T cells secrete IFNgamma and TNFalpha/beta, but not IL-4. |
| 1142 | 9421467 | We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. |
| 1143 | 9421467 | Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM. |
| 1144 | 9421467 | GAD-reactive CD4+ Th1 cells induce diabetes in NOD/SCID mice. |
| 1145 | 9421467 | Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. |
| 1146 | 9421467 | Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4+ T cell line, designated 5A, that expresses TCRs encoding Vbeta2 and Vbeta12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524-543. |
| 1147 | 9421467 | After antigen-specific stimulation, 5A T cells secrete IFNgamma and TNFalpha/beta, but not IL-4. |
| 1148 | 9421467 | We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. |
| 1149 | 9421467 | Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM. |
| 1150 | 9433472 | The prodromal period of insulin-dependent diabetes mellitus (IDDM) is characterized by circulating islet cell autoantibodies (ICA) and other beta cell specific autoantibodies. |
| 1151 | 9433472 | Despite biochemical characterization of the major beta cell autoantigens insulin, glutamic acid decarboxylase and protein tyrosine phosphatase and development of the respective antibody assays, ICA has remained the standard in IDDM prediction. |
| 1152 | 9433472 | Of 57 consecutive new-onset IDDM patients, 55 (96.5%) were ICA positive in the new assay while 51 (89.5%) were positive in the conventional assay suggesting that the sensitivity of TRFI exceeds that of the IAA, GAD65 and IA-2 autoantibody assays combined. |
| 1153 | 9447280 | Autoantibody against IA-2 improves the test sensitivity for insulin-dependent diabetes mellitus in Japanese patients of child onset. |
| 1154 | 9447280 | We previously reported that IA-2 autoantibodies (Ab) facilitated the diagnosis of Japanese insulin-dependent diabetes mellitus (IDDM), but the number tested was not large enough to investigate whether IA-2Ab can improve the diagnostic accuracy. |
| 1155 | 9447280 | In this report, sera from 78 patients with less than 2 year-disease duration (the mean (range) ages were 19.2 (6-52) years old) were tested in order to clarify that the combination of IA-2Ab and glutamic acid decarboxylase 65 (GAD65)Ab would improve the test sensitivity for IDDM. |
| 1156 | 9447280 | We confirmed that IA-2 antibody was detected in IDDM among Japanese, as seen in Caucasians, but the test sensitivity was improved only in young IDDM patients among Japanese. |
| 1157 | 9480718 | Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. |
| 1158 | 9480718 | There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. |
| 1159 | 9480718 | We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. |
| 1160 | 9480718 | ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. |
| 1161 | 9480718 | The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). |
| 1162 | 9480718 | Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). |
| 1163 | 9480718 | Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. |
| 1164 | 9480718 | Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. |
| 1165 | 9480718 | There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. |
| 1166 | 9480718 | We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. |
| 1167 | 9480718 | ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. |
| 1168 | 9480718 | The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). |
| 1169 | 9480718 | Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). |
| 1170 | 9480718 | Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. |
| 1171 | 9480718 | Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. |
| 1172 | 9480718 | There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. |
| 1173 | 9480718 | We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. |
| 1174 | 9480718 | ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. |
| 1175 | 9480718 | The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). |
| 1176 | 9480718 | Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). |
| 1177 | 9480718 | Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. |
| 1178 | 9480718 | Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. |
| 1179 | 9480718 | There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. |
| 1180 | 9480718 | We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. |
| 1181 | 9480718 | ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. |
| 1182 | 9480718 | The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). |
| 1183 | 9480718 | Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). |
| 1184 | 9480718 | Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. |
| 1185 | 9480718 | Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. |
| 1186 | 9480718 | There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. |
| 1187 | 9480718 | We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. |
| 1188 | 9480718 | ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. |
| 1189 | 9480718 | The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). |
| 1190 | 9480718 | Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). |
| 1191 | 9480718 | Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. |
| 1192 | 9480718 | Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. |
| 1193 | 9480718 | There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. |
| 1194 | 9480718 | We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. |
| 1195 | 9480718 | ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. |
| 1196 | 9480718 | The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). |
| 1197 | 9480718 | Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). |
| 1198 | 9480718 | Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. |
| 1199 | 9483382 | Determination of GAD autoantibodies was performed using an enzyme immunoassay (Varelisa) which is based on a recombinant human GAD65. |
| 1200 | 9498628 | It has been proposed that molecular mimicry between protein 2C (p2C) of coxsackie virus B4 and the autoantigen glutamic acid decarboxylase (GAD65) plays a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 1201 | 9498628 | Therefore, we tested whether the PEVKEK motif can bind to the IDDM-associated HLA-DR1, -DR3 and -DR4 molecules. |
| 1202 | 9498778 | A peptide binding motif for HLA-DQA1*0102/DQB1*0602, the class II MHC molecule associated with dominant protection in insulin-dependent diabetes mellitus. |
| 1203 | 9498778 | HLA-DQA1*0102/DQB1*0602 (DQ0602) is observed at a decreased frequency in insulin-dependent diabetes mellitus in different ethnic groups, suggesting a protective role for DQ0602. |
| 1204 | 9498778 | Peptides 11 amino acids long were selected from GAD65, IA-2, and proinsulin, that contained the DQ0602 peptide binding motif. |
| 1205 | 9513413 | [Autoantibodies against GAD and GAD65]. |
| 1206 | 9528889 | Glutamic acid decarboxylase-65 (GAD-65) is a major target for autoantibodies and autoreactive T cells in patients with insulin-dependent diabetes mellitus (IDDM). |
| 1207 | 9528889 | The epitope specificities of autoantibodies to GAD in IDDM and SMS have been well documented, but the locations of autoantibody epitopes of GAD in PE patients have not been mapped. |
| 1208 | 9542768 | The recent cloning and recombinant expression of novel islet autoantigens [glutamic acid decarboxylase (GAD) 65 and islet-cell autoantibody 512 (ICA512)] has made possible the determination of whether the quantitative expression of autoantibodies to these molecules is correlated with age of diabetes onset and rate of progression to diabetes, similar to insulin autoantibodies (IAAs). |
| 1209 | 9542768 | We measured autoantibodies reacting with GAD65 (GAD65AA), ICA512 (ICA512AA), and insulin in patients who recently had received a diagnosis of diabetes and in first-degree relatives prospectively identified and then followed because of the expression of high titers of ICA. |
| 1210 | 9550282 | Whereas we and others have observed a delay in the onset of diabetes in NOD mice that have been fed with insulin from early life, we report here for the first time that feedings with porcine GAD65 alone (p = 0.226) or in combination with insulin (p = 0.011), have anti-diabetic effects in a prolonged study period (>400 days). |
| 1211 | 9550282 | IFN-gamma mRNA levels were downregulated in the islet infiltrates following oral antigen treatments while IL-2 and TNF-beta were expressed in all instances. |
| 1212 | 9550282 | We also observed that I.V. human recombinant GAD65, and porcine GAD given at weaning, delayed diabetes onset (p = 0.004) while similar treatments with a variety of inactive insulin preparations were generally ineffective. |
| 1213 | 9550282 | Whereas we and others have observed a delay in the onset of diabetes in NOD mice that have been fed with insulin from early life, we report here for the first time that feedings with porcine GAD65 alone (p = 0.226) or in combination with insulin (p = 0.011), have anti-diabetic effects in a prolonged study period (>400 days). |
| 1214 | 9550282 | IFN-gamma mRNA levels were downregulated in the islet infiltrates following oral antigen treatments while IL-2 and TNF-beta were expressed in all instances. |
| 1215 | 9550282 | We also observed that I.V. human recombinant GAD65, and porcine GAD given at weaning, delayed diabetes onset (p = 0.004) while similar treatments with a variety of inactive insulin preparations were generally ineffective. |
| 1216 | 9550329 | Association between autoantibody markers and subtypes of DR4 and DR4-DQ in Swedish children with insulin-dependent diabetes reveals closer association of tyrosine pyrophosphatase autoimmunity with DR4 than DQ8. |
| 1217 | 9550329 | HLA DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) are positively and DQA1*0102-DQB1*0602 (DQ6) negatively associated with IDDM. |
| 1218 | 9550329 | The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0-15 years. |
| 1219 | 9594623 | [GAD antibody in IDDM]. |
| 1220 | 9594623 | Two forms of GAD (GAD65 and GAD67) are known to be expressed in human tissues and GAD65 is predominantly expressed in pancreatic beta-cells. |
| 1221 | 9594623 | Recent findings revealed that GAD functions as an autoantigen in human autoimmunity, especially in insulin-dependent diabetes mellitus (IDDM). |
| 1222 | 9594623 | GAD is a key antigen for the development of autoimmunity against beta-cells and the production of GADAb precedes other autoantibodies such as IAA and ICA512/IA-2Ab prior to the clinical onset of IDDM. |
| 1223 | 9604865 | IDDM is a T-cell-mediated autoimmune disease in which the insulin-producing beta-cells are destroyed. |
| 1224 | 9604865 | Furthermore, suppression of the diabetogenic response is mediated by the induction of GAD65-specific CD4+ regulatory T-cells. |
| 1225 | 9628269 | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM), but little is known about its regulation and function in islet cells. |
| 1226 | 9628269 | In islets incubated in high glucose culture medium there was an increase in GAD activity, GAD65 and GAD67 protein levels compared to low-glucose conditions; however, even in high glucose, GVG still significantly suppressed GAD activity and GAD67 expression. |
| 1227 | 9628269 | Taken together, these results suggest that GVG potentially could be of use to decrease GAD expression in islet cells and consequently to deviate/inhibit the autoimmune response against the beta cells seen in IDDM. |
| 1228 | 9645372 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a predominantly non-hereditary etiology that results in a destruction of pancreatic beta cells by autoaggressive T lymphocytes. |
| 1229 | 9645372 | We determined sequential epitope motifs to search for mimicry peptides stimulating T cell lines specific for two epitopes derived from the IDDM autoantigen 65-kDa glutamic acid decarboxylase (GAD65). |
| 1230 | 9645372 | These were GAD65 (88-99), presented by HLA-DRB1*0101, and GAD65 (248-257), presented by HLA-DRB5*0101. |
| 1231 | 9645372 | Our results demonstrate that mono- and polyclonal GAD65-specific T cells from IDDM patients can be stimulated by viral and bacterial peptides with little apparent sequence homology with autoantigenic epitopes. |
| 1232 | 9645372 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a predominantly non-hereditary etiology that results in a destruction of pancreatic beta cells by autoaggressive T lymphocytes. |
| 1233 | 9645372 | We determined sequential epitope motifs to search for mimicry peptides stimulating T cell lines specific for two epitopes derived from the IDDM autoantigen 65-kDa glutamic acid decarboxylase (GAD65). |
| 1234 | 9645372 | These were GAD65 (88-99), presented by HLA-DRB1*0101, and GAD65 (248-257), presented by HLA-DRB5*0101. |
| 1235 | 9645372 | Our results demonstrate that mono- and polyclonal GAD65-specific T cells from IDDM patients can be stimulated by viral and bacterial peptides with little apparent sequence homology with autoantigenic epitopes. |
| 1236 | 9645372 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a predominantly non-hereditary etiology that results in a destruction of pancreatic beta cells by autoaggressive T lymphocytes. |
| 1237 | 9645372 | We determined sequential epitope motifs to search for mimicry peptides stimulating T cell lines specific for two epitopes derived from the IDDM autoantigen 65-kDa glutamic acid decarboxylase (GAD65). |
| 1238 | 9645372 | These were GAD65 (88-99), presented by HLA-DRB1*0101, and GAD65 (248-257), presented by HLA-DRB5*0101. |
| 1239 | 9645372 | Our results demonstrate that mono- and polyclonal GAD65-specific T cells from IDDM patients can be stimulated by viral and bacterial peptides with little apparent sequence homology with autoantigenic epitopes. |
| 1240 | 9650286 | Glutamic acid decarboxylase (GAD) is one of the major autoantigens found in insulin-dependent (Type 1) diabetes mellitus (IDDM). |
| 1241 | 9650286 | A novel hybrid form of GAD was created by fusing amino acids 1-101 of the human GAD67 protein to amino acids 96-585 of the human GAD65 protein. |
| 1242 | 9671127 | A simple and rapid microSepharose assay for GAD65 and ICA512 autoantibodies in diabetes. |
| 1243 | 9698109 | To study systematically the linear epitope specificity of anti-glutamic acid decarboxylase (GAD) autoantibodies associated with insulin-dependent diabetes mellitus (IDDM), we produced 93 overlapping 12-residue synthetic peptides derived from the sequence of the human GAD65 protein and covering the entire length of the protein. |
| 1244 | 9698109 | These peptides were used as antigens in an enzyme immunoassay to screen the sera from 10 IDDM patients, all of which contained at high level autoantibodies directed against GAD65. |
| 1245 | 9698109 | Two of the peptide-reactive IDDM sera, which also bound denatured recombinant GAD65 on western blots, had the highest titers of anti-GAD antibodies in ELISA assay. |
| 1246 | 9698109 | To study systematically the linear epitope specificity of anti-glutamic acid decarboxylase (GAD) autoantibodies associated with insulin-dependent diabetes mellitus (IDDM), we produced 93 overlapping 12-residue synthetic peptides derived from the sequence of the human GAD65 protein and covering the entire length of the protein. |
| 1247 | 9698109 | These peptides were used as antigens in an enzyme immunoassay to screen the sera from 10 IDDM patients, all of which contained at high level autoantibodies directed against GAD65. |
| 1248 | 9698109 | Two of the peptide-reactive IDDM sera, which also bound denatured recombinant GAD65 on western blots, had the highest titers of anti-GAD antibodies in ELISA assay. |
| 1249 | 9698109 | To study systematically the linear epitope specificity of anti-glutamic acid decarboxylase (GAD) autoantibodies associated with insulin-dependent diabetes mellitus (IDDM), we produced 93 overlapping 12-residue synthetic peptides derived from the sequence of the human GAD65 protein and covering the entire length of the protein. |
| 1250 | 9698109 | These peptides were used as antigens in an enzyme immunoassay to screen the sera from 10 IDDM patients, all of which contained at high level autoantibodies directed against GAD65. |
| 1251 | 9698109 | Two of the peptide-reactive IDDM sera, which also bound denatured recombinant GAD65 on western blots, had the highest titers of anti-GAD antibodies in ELISA assay. |
| 1252 | 9699085 | Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. |
| 1253 | 9707599 | Glutamic acid decarboxylase (GAD)65 is a pancreatic beta cell autoantigen implicated as a target of T cells that initiate and sustain insulin-dependent diabetes mellitus (IDDM) in humans and in non-obese diabetic (NOD) mice. |
| 1254 | 9707599 | In an attempt to establish immunological tolerance toward GAD65 in NOD mice, and thereby to test the importance of GAD in IDDM, we generated three lines transgenic for murine GAD65 driven by a major histocompatibility complex class I promoter. |
| 1255 | 9707599 | Thus, the failure of NOD mice to develop tolerance toward GAD65 reflects at minimum a basic defect in central tolerance, not seen in animals not predisposed to IDDM. |
| 1256 | 9707599 | Glutamic acid decarboxylase (GAD)65 is a pancreatic beta cell autoantigen implicated as a target of T cells that initiate and sustain insulin-dependent diabetes mellitus (IDDM) in humans and in non-obese diabetic (NOD) mice. |
| 1257 | 9707599 | In an attempt to establish immunological tolerance toward GAD65 in NOD mice, and thereby to test the importance of GAD in IDDM, we generated three lines transgenic for murine GAD65 driven by a major histocompatibility complex class I promoter. |
| 1258 | 9707599 | Thus, the failure of NOD mice to develop tolerance toward GAD65 reflects at minimum a basic defect in central tolerance, not seen in animals not predisposed to IDDM. |
| 1259 | 9757911 | Characterization of self-glutamic acid decarboxylase 65-reactive CD4+ T-cell clones established from Japanese patients with insulin-dependent diabetes mellitus. |
| 1260 | 9757911 | To investigate autoimmunity to glutamic acid decarboxylase (GAD) 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes), we established seven CD4+ T-cell clones, by stimulating peripheral blood mononuclear cells (PBMC) of six IDDM patients, using a mixture of overlapping human GAD65 peptides. |
| 1261 | 9768369 | Antibodies to glutamic acid decarboxylase (GAD) in non-obese Japanese diabetics without insulin therapy: a comparison of two commercial RIA kits based on recombinant and pig brain GAD. |
| 1262 | 9768369 | To compare the clinical usefulness of commercial radioimmunoassay (RIA) kits based on recombinant and pig brain GAD, we measured glutamic acid decarboxylase autoantibody (GADAb) titers in 125 non-obese (body mass index < 24) Japanese diabetics without insulin therapy using two commercial RIA kits based on recombinant human (rh) GAD65 (GADAb Cosmic) and purified pig brain native GAD (RIP Anti-GAD Hoechst). |
| 1263 | 9768369 | Based on the binding study after pre-incubation of unlabeled GADs, these low titrated GADAb were elucidated to be true specific reactions to rh GAD65 alone. |
| 1264 | 9768369 | These findings suggest that the measurement of GADAb using a commercial assay kit with rh GAD65 may be more useful to detect non-insulin-dependent type I diabetics among non-obese patients than using a commercial kit with purified pig brain native GAD, especially among those with low GADAb titers. |
| 1265 | 9768369 | Antibodies to glutamic acid decarboxylase (GAD) in non-obese Japanese diabetics without insulin therapy: a comparison of two commercial RIA kits based on recombinant and pig brain GAD. |
| 1266 | 9768369 | To compare the clinical usefulness of commercial radioimmunoassay (RIA) kits based on recombinant and pig brain GAD, we measured glutamic acid decarboxylase autoantibody (GADAb) titers in 125 non-obese (body mass index < 24) Japanese diabetics without insulin therapy using two commercial RIA kits based on recombinant human (rh) GAD65 (GADAb Cosmic) and purified pig brain native GAD (RIP Anti-GAD Hoechst). |
| 1267 | 9768369 | Based on the binding study after pre-incubation of unlabeled GADs, these low titrated GADAb were elucidated to be true specific reactions to rh GAD65 alone. |
| 1268 | 9768369 | These findings suggest that the measurement of GADAb using a commercial assay kit with rh GAD65 may be more useful to detect non-insulin-dependent type I diabetics among non-obese patients than using a commercial kit with purified pig brain native GAD, especially among those with low GADAb titers. |
| 1269 | 9768369 | Antibodies to glutamic acid decarboxylase (GAD) in non-obese Japanese diabetics without insulin therapy: a comparison of two commercial RIA kits based on recombinant and pig brain GAD. |
| 1270 | 9768369 | To compare the clinical usefulness of commercial radioimmunoassay (RIA) kits based on recombinant and pig brain GAD, we measured glutamic acid decarboxylase autoantibody (GADAb) titers in 125 non-obese (body mass index < 24) Japanese diabetics without insulin therapy using two commercial RIA kits based on recombinant human (rh) GAD65 (GADAb Cosmic) and purified pig brain native GAD (RIP Anti-GAD Hoechst). |
| 1271 | 9768369 | Based on the binding study after pre-incubation of unlabeled GADs, these low titrated GADAb were elucidated to be true specific reactions to rh GAD65 alone. |
| 1272 | 9768369 | These findings suggest that the measurement of GADAb using a commercial assay kit with rh GAD65 may be more useful to detect non-insulin-dependent type I diabetics among non-obese patients than using a commercial kit with purified pig brain native GAD, especially among those with low GADAb titers. |
| 1273 | 9771977 | Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of the autoimmune-mediated beta-cell destruction in insulin-dependent (Type I) diabetes. |
| 1274 | 9771977 | However, these autoantibodies are also found in patients with Stiff-man syndrome (SMS) without onset of diabetes and some diabetic patients who initially present as non-insulin dependent (Type II) diabetes later becoming insulin-dependent, called as latent autoimmune diabetes in adults (LADA). |
| 1275 | 9771977 | The SMS sera completely abolished the GAD binding of all three monoclonals, reflecting a broader repertoire including an immune response against the IDDM-E1, a conformation-dependent GAD65 epitope region, also revealed if the SMS sera are diluted to equivalent antibody concentrations. |
| 1276 | 9771977 | In summary, our results show that diabetes-associated GAD autoantibodies even in adult patients with a late autoimmune process preferentially recognize a conformation-dependent middle GAD65 region. |
| 1277 | 9771977 | Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of the autoimmune-mediated beta-cell destruction in insulin-dependent (Type I) diabetes. |
| 1278 | 9771977 | However, these autoantibodies are also found in patients with Stiff-man syndrome (SMS) without onset of diabetes and some diabetic patients who initially present as non-insulin dependent (Type II) diabetes later becoming insulin-dependent, called as latent autoimmune diabetes in adults (LADA). |
| 1279 | 9771977 | The SMS sera completely abolished the GAD binding of all three monoclonals, reflecting a broader repertoire including an immune response against the IDDM-E1, a conformation-dependent GAD65 epitope region, also revealed if the SMS sera are diluted to equivalent antibody concentrations. |
| 1280 | 9771977 | In summary, our results show that diabetes-associated GAD autoantibodies even in adult patients with a late autoimmune process preferentially recognize a conformation-dependent middle GAD65 region. |
| 1281 | 9776711 | Glutamic acid decarboxylase autoimmunity was investigated by immunizing female BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. |
| 1282 | 9776711 | Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cytokine secretion. |
| 1283 | 9776711 | IL-4 and IL-10 were only detected after two immunizations with higher levels in BALB/c, NMRI and NOD mice, compared to C57B1/6 mice. |
| 1284 | 9776711 | In NOD mice, peri-insulitis was detected in all groups, but less so in GAD65 and bovine serum albumin (BSA) immunized animals. |
| 1285 | 9776711 | Glutamic acid decarboxylase autoimmunity was investigated by immunizing female BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. |
| 1286 | 9776711 | Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cytokine secretion. |
| 1287 | 9776711 | IL-4 and IL-10 were only detected after two immunizations with higher levels in BALB/c, NMRI and NOD mice, compared to C57B1/6 mice. |
| 1288 | 9776711 | In NOD mice, peri-insulitis was detected in all groups, but less so in GAD65 and bovine serum albumin (BSA) immunized animals. |
| 1289 | 9776711 | Glutamic acid decarboxylase autoimmunity was investigated by immunizing female BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. |
| 1290 | 9776711 | Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cytokine secretion. |
| 1291 | 9776711 | IL-4 and IL-10 were only detected after two immunizations with higher levels in BALB/c, NMRI and NOD mice, compared to C57B1/6 mice. |
| 1292 | 9776711 | In NOD mice, peri-insulitis was detected in all groups, but less so in GAD65 and bovine serum albumin (BSA) immunized animals. |
| 1293 | 9840449 | Peptide from glutamic acid decarboxylase similar to coxsackie B virus stimulates IFN-gamma mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus. |
| 1294 | 9840449 | CD4+ or Th-lymphocytes will be activated after stimulation resulting in interferon-gamma (IFN-gamma) production by Th1-like lymphocytes and/or interleukin-4 (IL-4) secretion from Th2-like lymphocytes. |
| 1295 | 9840449 | In this study we have shown that this peptide activates Th1-like lymphocytes which produce increased amounts of IFN-gamma mRNA, but seldom mRNA for IL-4. |
| 1296 | 9840449 | In conclusion, we suggest that GAD65 is involved in the development of type 1 diabetes and that the Th1-response may play a role in the destruction of beta cells. |
| 1297 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1298 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1299 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1300 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1301 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1302 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1303 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1304 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1305 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1306 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1307 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1308 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1309 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1310 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1311 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1312 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1313 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1314 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1315 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1316 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1317 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1318 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1319 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1320 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1321 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1322 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1323 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1324 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1325 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1326 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1327 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1328 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1329 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1330 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1331 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1332 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1333 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1334 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1335 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1336 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1337 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1338 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1339 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1340 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1341 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1342 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1343 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1344 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1345 | 9892508 | Glutamic acid decarboxylase (GAD) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). |
| 1346 | 9892508 | Two GAD isoforms exist, GAD65 and GAD67, which differ mostly in the first 100 amino acids of the amino terminus. |
| 1347 | 9892508 | IDDM sera are predominantly reactive with GAD65 but autoepitopes have been localised only to regions of GAD65 highly homologous with GAD67. |
| 1348 | 9892508 | In this study we investigated the contribution of the amino terminus to the IDDM epitope on GAD65, in order to test whether this region of GAD could explain the difference in reactivity between GAD65 and GAD67. |
| 1349 | 9892508 | A recombinant hybrid GAD molecule consisting of amino acids 1-101 of GAD67 and 96-585 of GAD65 was constructed and a truncated GAD65 was also constructed consisting of amino acids 98-585 of GAD65. |
| 1350 | 9892508 | The reactivity with the hybrid GAD molecule, GAD65 and GAD67, and truncated GAD65 was examined by radioimmunoprecipitation using 50 IDDM sera with known reactivity to purified porcine brain GAD. |
| 1351 | 9892508 | Over 90% of the IDDM sera were reactive with the hybrid GAD molecule confirming that the amino terminus of GAD65 does not contribute to the autoepitope and that the IDDM epitope is localised to the middle and carboxyl terminal domains of GAD65. |
| 1352 | 9892508 | Furthermore, evidence is presented that autoantibodies to GAD65 in IDDM sera react with an epitope formed on a dimeric configuration of the molecule. |
| 1353 | 10052685 | Lack of association between CTLA-4 gene polymorphism and IDDM in Japanese subjects. |
| 1354 | 10052685 | Susceptibility to insulin-dependent diabetes mellitus (IDDM) is determined by both environmental and genetic factors. |
| 1355 | 10052685 | Recent studies have described linkage and association of IDDM to the CTLA-4 gene (IDDM12) in Caucasians. |
| 1356 | 10052685 | We investigated the distribution of a CTLA-4 gene polymorphism in 110 Japanese patients with IDDM and 200 control subjects. |
| 1357 | 10052685 | In 84 patients, we also investigated associations between this CTLA-4 gene polymorphism and GAD65 antibody positivity. |
| 1358 | 10052685 | There was no significant difference in the distribution of CTLA-4 alleles in patients and controls and no difference was observed in prevalence of CTLA-4 alleles when GAD65 antibody-positive and -negative individuals in the IDDM groups were compared. |
| 1359 | 10052685 | The present study did not support an association between the CTLA-4 gene and IDDM in the Japanese population. |
| 1360 | 10052685 | Lack of association between CTLA-4 gene polymorphism and IDDM in Japanese subjects. |
| 1361 | 10052685 | Susceptibility to insulin-dependent diabetes mellitus (IDDM) is determined by both environmental and genetic factors. |
| 1362 | 10052685 | Recent studies have described linkage and association of IDDM to the CTLA-4 gene (IDDM12) in Caucasians. |
| 1363 | 10052685 | We investigated the distribution of a CTLA-4 gene polymorphism in 110 Japanese patients with IDDM and 200 control subjects. |
| 1364 | 10052685 | In 84 patients, we also investigated associations between this CTLA-4 gene polymorphism and GAD65 antibody positivity. |
| 1365 | 10052685 | There was no significant difference in the distribution of CTLA-4 alleles in patients and controls and no difference was observed in prevalence of CTLA-4 alleles when GAD65 antibody-positive and -negative individuals in the IDDM groups were compared. |
| 1366 | 10052685 | The present study did not support an association between the CTLA-4 gene and IDDM in the Japanese population. |
| 1367 | 10078545 | Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4, DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice. |
| 1368 | 10078545 | To map T-cell epitopes for GAD65 restricted to the diabetes-associated DQ8 heterodimer, we generated transgenic NOD mice expressing HLA-DQ8 and human CD4 while having the mouse class II gene (IA(beta)) deleted. |
| 1369 | 10078545 | Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4, DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice. |
| 1370 | 10078545 | To map T-cell epitopes for GAD65 restricted to the diabetes-associated DQ8 heterodimer, we generated transgenic NOD mice expressing HLA-DQ8 and human CD4 while having the mouse class II gene (IA(beta)) deleted. |
| 1371 | 10080840 | To investigate whether type 1 diabetes in man is associated with a preferential Th1/Th2 response, and whether autoantibodies to one of the main autoantigens would reflect such a response, we characterized the immunoglobulin isotype profile to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) in siblings to IDDM patients. |
| 1372 | 10080840 | The rank order of anti-GAD65 immunoglobulin isotypes was similar in the siblings before and at clinical onset of IDDM, IgG1 > IgG4 > IgM > IgE > IgA > IgG3 > IgG2, but markedly different in the individuals at low risk, IgG1 > IgM > IgE > IgG4 > IgG3 > IgA > IgG2. |
| 1373 | 10080840 | Based on these observations, we suggest that progression to clinical onset of IDDM is associated with a maturation and a decrease in the Th2 immune response against GAD65; findings which could have implications for future intervention and prediction strategies. |
| 1374 | 10080840 | To investigate whether type 1 diabetes in man is associated with a preferential Th1/Th2 response, and whether autoantibodies to one of the main autoantigens would reflect such a response, we characterized the immunoglobulin isotype profile to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) in siblings to IDDM patients. |
| 1375 | 10080840 | The rank order of anti-GAD65 immunoglobulin isotypes was similar in the siblings before and at clinical onset of IDDM, IgG1 > IgG4 > IgM > IgE > IgA > IgG3 > IgG2, but markedly different in the individuals at low risk, IgG1 > IgM > IgE > IgG4 > IgG3 > IgA > IgG2. |
| 1376 | 10080840 | Based on these observations, we suggest that progression to clinical onset of IDDM is associated with a maturation and a decrease in the Th2 immune response against GAD65; findings which could have implications for future intervention and prediction strategies. |
| 1377 | 10096794 | Towards a World Health Organization (WHO) approved standard sample for islet cell antibodies, GAD65 and IA-2 autoantibodies. |
| 1378 | 10194908 | The occurrence of type I diabetes is associated with autoimmunity against insulin, glutamate decarboxylase (GAD65) and the transmembrane protein IA-2. |
| 1379 | 10234796 | GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. |
| 1380 | 10234796 | After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. |
| 1381 | 10234796 | GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. |
| 1382 | 10234796 | After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. |
| 1383 | 10330299 | Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives. |
| 1384 | 10330300 | GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. |
| 1385 | 10330300 | To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. |
| 1386 | 10330300 | T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. |
| 1387 | 10330300 | These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). |
| 1388 | 10330300 | GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. |
| 1389 | 10330300 | To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. |
| 1390 | 10330300 | T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. |
| 1391 | 10330300 | These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). |
| 1392 | 10330300 | GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. |
| 1393 | 10330300 | To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. |
| 1394 | 10330300 | T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. |
| 1395 | 10330300 | These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). |
| 1396 | 10333047 | Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index. |
| 1397 | 10398550 | In addition, the purpose was to investigate if sample 673 could also serve as a standard for GAD65 and IA-2 antibodies. |
| 1398 | 10403912 | Autoantibodies and autoreactive T lymphocytes directed against several pancreatic beta cell proteins such as GAD65 have been identified in the circulation before and at the onset of clinical type 1 (insulin-dependent) diabetes. |
| 1399 | 10415012 | Peptide-based immunotherapy is one strategy by which to selectively suppress the T cell-mediated destruction of beta cells and treat insulin-dependent diabetes mellitus (IDDM). |
| 1400 | 10415012 | Here, we investigated whether a panel of T cell epitopes derived from the beta cell autoantigen glutamic acid decarboxylase 65 (GAD65) differ in their capacity to induce Th2 cell function in nonobese diabetic (NOD) mice and in turn prevent overt IDDM at different preclinical stages of disease development. |
| 1401 | 10415012 | Immunization with the GAD65-specific peptides did not block IDDM development in NOD mice deficient in IL-4 expression. |
| 1402 | 10415012 | These findings demonstrate that GAD65-specific peptide immunotherapy effectively suppresses progression to overt IDDM, requires the production of IL-4, and is dependent on the epitope targeted and the extent of preexisting beta cell autoimmunity in the recipient. |
| 1403 | 10415012 | Peptide-based immunotherapy is one strategy by which to selectively suppress the T cell-mediated destruction of beta cells and treat insulin-dependent diabetes mellitus (IDDM). |
| 1404 | 10415012 | Here, we investigated whether a panel of T cell epitopes derived from the beta cell autoantigen glutamic acid decarboxylase 65 (GAD65) differ in their capacity to induce Th2 cell function in nonobese diabetic (NOD) mice and in turn prevent overt IDDM at different preclinical stages of disease development. |
| 1405 | 10415012 | Immunization with the GAD65-specific peptides did not block IDDM development in NOD mice deficient in IL-4 expression. |
| 1406 | 10415012 | These findings demonstrate that GAD65-specific peptide immunotherapy effectively suppresses progression to overt IDDM, requires the production of IL-4, and is dependent on the epitope targeted and the extent of preexisting beta cell autoimmunity in the recipient. |
| 1407 | 10415012 | Peptide-based immunotherapy is one strategy by which to selectively suppress the T cell-mediated destruction of beta cells and treat insulin-dependent diabetes mellitus (IDDM). |
| 1408 | 10415012 | Here, we investigated whether a panel of T cell epitopes derived from the beta cell autoantigen glutamic acid decarboxylase 65 (GAD65) differ in their capacity to induce Th2 cell function in nonobese diabetic (NOD) mice and in turn prevent overt IDDM at different preclinical stages of disease development. |
| 1409 | 10415012 | Immunization with the GAD65-specific peptides did not block IDDM development in NOD mice deficient in IL-4 expression. |
| 1410 | 10415012 | These findings demonstrate that GAD65-specific peptide immunotherapy effectively suppresses progression to overt IDDM, requires the production of IL-4, and is dependent on the epitope targeted and the extent of preexisting beta cell autoimmunity in the recipient. |
| 1411 | 10415074 | Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401-positive individuals. |
| 1412 | 10415074 | When pulsed with the GAD protein, some DRB1*0401-positive B-LCL, which presented GAD65 274-286 epitope efficiently, were unable to present the GAD65 115-127 epitope. |
| 1413 | 10415074 | Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401-positive individuals. |
| 1414 | 10415074 | When pulsed with the GAD protein, some DRB1*0401-positive B-LCL, which presented GAD65 274-286 epitope efficiently, were unable to present the GAD65 115-127 epitope. |
| 1415 | 10433070 | Interleukin-1beta (IL-1beta) has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct islet cytotoxicity and alteration of islet cell antigen expression. |
| 1416 | 10433070 | We have previously demonstrated that IL-1beta inhibits glutamic acid decarboxylase-65 (GAD-65) and increases heat shock protein-70 (HSP-70) expression in islet cells. |
| 1417 | 10433070 | In this study we investigated the role of the NO pathway in mediating the effects of IL-1beta on GAD-65 and HSP-70 expression and on insulin secretion. |
| 1418 | 10433070 | Accumulated nitrite production, insulin release and islet expression of GAD-65 and HSP-70 were measured. |
| 1419 | 10433070 | We found that (1) IL-1beta at 10 U/ml increased nitrite production, inhibited insulin release, increased HSP-70 expression and decreased GAD-65 expression. (2) AG alone at 1 mM/ml had no effect on nitrite production, insulin release, GAD-65 and HSP-70 expression. (3) In combination, AG completely blocked IL-1beta increased nitrite production, reversed IL-1beta inhibited insulin release by approximately 50%, completely reversed IL-1beta increased HSP-70 expression, but did not reverse IL-1beta inhibited GAD-65 expression. |
| 1420 | 10433070 | Our findings indicate that the effect of IL-1beta on HSP-70 expression is mediated by NO production, whereas a NO-independent pathway is involved in the effect of IL-1beta on GAD-65 expression and insulin secretion. |
| 1421 | 10433070 | Interleukin-1beta (IL-1beta) has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct islet cytotoxicity and alteration of islet cell antigen expression. |
| 1422 | 10433070 | We have previously demonstrated that IL-1beta inhibits glutamic acid decarboxylase-65 (GAD-65) and increases heat shock protein-70 (HSP-70) expression in islet cells. |
| 1423 | 10433070 | In this study we investigated the role of the NO pathway in mediating the effects of IL-1beta on GAD-65 and HSP-70 expression and on insulin secretion. |
| 1424 | 10433070 | Accumulated nitrite production, insulin release and islet expression of GAD-65 and HSP-70 were measured. |
| 1425 | 10433070 | We found that (1) IL-1beta at 10 U/ml increased nitrite production, inhibited insulin release, increased HSP-70 expression and decreased GAD-65 expression. (2) AG alone at 1 mM/ml had no effect on nitrite production, insulin release, GAD-65 and HSP-70 expression. (3) In combination, AG completely blocked IL-1beta increased nitrite production, reversed IL-1beta inhibited insulin release by approximately 50%, completely reversed IL-1beta increased HSP-70 expression, but did not reverse IL-1beta inhibited GAD-65 expression. |
| 1426 | 10433070 | Our findings indicate that the effect of IL-1beta on HSP-70 expression is mediated by NO production, whereas a NO-independent pathway is involved in the effect of IL-1beta on GAD-65 expression and insulin secretion. |
| 1427 | 10433070 | Interleukin-1beta (IL-1beta) has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct islet cytotoxicity and alteration of islet cell antigen expression. |
| 1428 | 10433070 | We have previously demonstrated that IL-1beta inhibits glutamic acid decarboxylase-65 (GAD-65) and increases heat shock protein-70 (HSP-70) expression in islet cells. |
| 1429 | 10433070 | In this study we investigated the role of the NO pathway in mediating the effects of IL-1beta on GAD-65 and HSP-70 expression and on insulin secretion. |
| 1430 | 10433070 | Accumulated nitrite production, insulin release and islet expression of GAD-65 and HSP-70 were measured. |
| 1431 | 10433070 | We found that (1) IL-1beta at 10 U/ml increased nitrite production, inhibited insulin release, increased HSP-70 expression and decreased GAD-65 expression. (2) AG alone at 1 mM/ml had no effect on nitrite production, insulin release, GAD-65 and HSP-70 expression. (3) In combination, AG completely blocked IL-1beta increased nitrite production, reversed IL-1beta inhibited insulin release by approximately 50%, completely reversed IL-1beta increased HSP-70 expression, but did not reverse IL-1beta inhibited GAD-65 expression. |
| 1432 | 10433070 | Our findings indicate that the effect of IL-1beta on HSP-70 expression is mediated by NO production, whereas a NO-independent pathway is involved in the effect of IL-1beta on GAD-65 expression and insulin secretion. |
| 1433 | 10433070 | Interleukin-1beta (IL-1beta) has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct islet cytotoxicity and alteration of islet cell antigen expression. |
| 1434 | 10433070 | We have previously demonstrated that IL-1beta inhibits glutamic acid decarboxylase-65 (GAD-65) and increases heat shock protein-70 (HSP-70) expression in islet cells. |
| 1435 | 10433070 | In this study we investigated the role of the NO pathway in mediating the effects of IL-1beta on GAD-65 and HSP-70 expression and on insulin secretion. |
| 1436 | 10433070 | Accumulated nitrite production, insulin release and islet expression of GAD-65 and HSP-70 were measured. |
| 1437 | 10433070 | We found that (1) IL-1beta at 10 U/ml increased nitrite production, inhibited insulin release, increased HSP-70 expression and decreased GAD-65 expression. (2) AG alone at 1 mM/ml had no effect on nitrite production, insulin release, GAD-65 and HSP-70 expression. (3) In combination, AG completely blocked IL-1beta increased nitrite production, reversed IL-1beta inhibited insulin release by approximately 50%, completely reversed IL-1beta increased HSP-70 expression, but did not reverse IL-1beta inhibited GAD-65 expression. |
| 1438 | 10433070 | Our findings indicate that the effect of IL-1beta on HSP-70 expression is mediated by NO production, whereas a NO-independent pathway is involved in the effect of IL-1beta on GAD-65 expression and insulin secretion. |
| 1439 | 10433070 | Interleukin-1beta (IL-1beta) has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct islet cytotoxicity and alteration of islet cell antigen expression. |
| 1440 | 10433070 | We have previously demonstrated that IL-1beta inhibits glutamic acid decarboxylase-65 (GAD-65) and increases heat shock protein-70 (HSP-70) expression in islet cells. |
| 1441 | 10433070 | In this study we investigated the role of the NO pathway in mediating the effects of IL-1beta on GAD-65 and HSP-70 expression and on insulin secretion. |
| 1442 | 10433070 | Accumulated nitrite production, insulin release and islet expression of GAD-65 and HSP-70 were measured. |
| 1443 | 10433070 | We found that (1) IL-1beta at 10 U/ml increased nitrite production, inhibited insulin release, increased HSP-70 expression and decreased GAD-65 expression. (2) AG alone at 1 mM/ml had no effect on nitrite production, insulin release, GAD-65 and HSP-70 expression. (3) In combination, AG completely blocked IL-1beta increased nitrite production, reversed IL-1beta inhibited insulin release by approximately 50%, completely reversed IL-1beta increased HSP-70 expression, but did not reverse IL-1beta inhibited GAD-65 expression. |
| 1444 | 10433070 | Our findings indicate that the effect of IL-1beta on HSP-70 expression is mediated by NO production, whereas a NO-independent pathway is involved in the effect of IL-1beta on GAD-65 expression and insulin secretion. |
| 1445 | 10439311 | CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. |
| 1446 | 10439311 | To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. |
| 1447 | 10439311 | Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. |
| 1448 | 10439311 | The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. |
| 1449 | 10439311 | The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. |
| 1450 | 10439311 | Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. |
| 1451 | 10439311 | CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. |
| 1452 | 10439311 | To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. |
| 1453 | 10439311 | Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. |
| 1454 | 10439311 | The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. |
| 1455 | 10439311 | The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. |
| 1456 | 10439311 | Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. |
| 1457 | 10439311 | CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. |
| 1458 | 10439311 | To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. |
| 1459 | 10439311 | Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. |
| 1460 | 10439311 | The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. |
| 1461 | 10439311 | The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. |
| 1462 | 10439311 | Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. |
| 1463 | 10439311 | CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. |
| 1464 | 10439311 | To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. |
| 1465 | 10439311 | Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. |
| 1466 | 10439311 | The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. |
| 1467 | 10439311 | The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. |
| 1468 | 10439311 | Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. |
| 1469 | 10439311 | CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. |
| 1470 | 10439311 | To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. |
| 1471 | 10439311 | Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. |
| 1472 | 10439311 | The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. |
| 1473 | 10439311 | The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. |
| 1474 | 10439311 | Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. |
| 1475 | 10439311 | CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. |
| 1476 | 10439311 | To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. |
| 1477 | 10439311 | Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. |
| 1478 | 10439311 | The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. |
| 1479 | 10439311 | The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. |
| 1480 | 10439311 | Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. |
| 1481 | 10459165 | Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). |
| 1482 | 10459165 | In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. |
| 1483 | 10459165 | Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. |
| 1484 | 10459165 | CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. |
| 1485 | 10459165 | Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). |
| 1486 | 10459165 | A correlation was not found between antibodies against GAD(65) and p2C. |
| 1487 | 10459165 | Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). |
| 1488 | 10459165 | In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. |
| 1489 | 10459165 | Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. |
| 1490 | 10459165 | CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. |
| 1491 | 10459165 | Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). |
| 1492 | 10459165 | A correlation was not found between antibodies against GAD(65) and p2C. |
| 1493 | 10459165 | Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). |
| 1494 | 10459165 | In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. |
| 1495 | 10459165 | Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. |
| 1496 | 10459165 | CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. |
| 1497 | 10459165 | Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). |
| 1498 | 10459165 | A correlation was not found between antibodies against GAD(65) and p2C. |
| 1499 | 10459165 | Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). |
| 1500 | 10459165 | In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. |
| 1501 | 10459165 | Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. |
| 1502 | 10459165 | CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. |
| 1503 | 10459165 | Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). |
| 1504 | 10459165 | A correlation was not found between antibodies against GAD(65) and p2C. |
| 1505 | 10459165 | Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). |
| 1506 | 10459165 | In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. |
| 1507 | 10459165 | Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. |
| 1508 | 10459165 | CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. |
| 1509 | 10459165 | Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). |
| 1510 | 10459165 | A correlation was not found between antibodies against GAD(65) and p2C. |
| 1511 | 10459165 | Analysis of antibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). |
| 1512 | 10459165 | In addition, a correlation of antibodies against CVB4 p2C and GAD(65) was studied in diabetes patients and in healthy controls. |
| 1513 | 10459165 | Antibody reactivity against CVB proteins was detected by immunoprecipitation of [(35)S]-methionine-labelled viral proteins and GAD(65) antibodies were measured in a quantitative radio-immunoassay. |
| 1514 | 10459165 | CVB4 p2C-specific antibodies were not only detectable in GAD(65) antibody-positive diabetes patients but also in GAD(65) antibody-negative healthy blood donors. |
| 1515 | 10459165 | Furthermore, GAD(65) antibodies could not be detected in p2C-positive subjects who had various enterovirus infections, indicating that an antibody response to CVB4 p2C does not necessarily induce a cross-reactive immune response against GAD(65). |
| 1516 | 10459165 | A correlation was not found between antibodies against GAD(65) and p2C. |
| 1517 | 10512357 | Identification of peptides from autoantigens GAD65 and IA-2 that bind to HLA class II molecules predisposing to or protecting from type 1 diabetes. |
| 1518 | 10512357 | We report clustering of binding peptides in the COOH-terminal regions of GAD65 and IA-2, as well as highly promiscuous binding patterns of some peptides. |
| 1519 | 10512357 | Our results demonstrate that most peptides derived from the GAD and IA-2 autoantigens can bind to both type 1 diabetes-predisposing and type 1 diabetes-protective HLA molecules, although some exceptions were observed. |
| 1520 | 10512357 | The binding inventory presented here for GAD and IA-2 peptides can be useful for mapping natural epitopes and predicting peptide-specific responses induced by preventive immunization. |
| 1521 | 10512357 | Identification of peptides from autoantigens GAD65 and IA-2 that bind to HLA class II molecules predisposing to or protecting from type 1 diabetes. |
| 1522 | 10512357 | We report clustering of binding peptides in the COOH-terminal regions of GAD65 and IA-2, as well as highly promiscuous binding patterns of some peptides. |
| 1523 | 10512357 | Our results demonstrate that most peptides derived from the GAD and IA-2 autoantigens can bind to both type 1 diabetes-predisposing and type 1 diabetes-protective HLA molecules, although some exceptions were observed. |
| 1524 | 10512357 | The binding inventory presented here for GAD and IA-2 peptides can be useful for mapping natural epitopes and predicting peptide-specific responses induced by preventive immunization. |
| 1525 | 10580419 | We show that antibodies present in the sera of newly diagnosed type 1 diabetic patients recognize BSDL and more specifically the COOH-terminal mucin-like region of the protein. |
| 1526 | 10580419 | Therefore, we engineered the COOH-terminal peptide of BSDL and demonstrated that autoreactivity was linked to specific glycosylation sites by at least two glycosyltransferases: the Core 2 beta(1-6)N-acetylglucosaminyltransferase and the alpha(1-3) fucosyltransferase FUT7. |
| 1527 | 10580419 | Interestingly, two prediabetic individuals were already positive for anti-BSDL antibodies (Abs), while islet cell cytoplasmic Abs and antibodies to GAD65, IA-2, and insulin were not detected. |
| 1528 | 10586096 | Most (78-91%) patient and sib responses to glutamate decarboxylase of 65 kDa (GAD65), islet cell cytoplasmic autoantibody (ICA) 69, diabetes-associated T cell epitopes in ICA69 (Tep69), and heat shock protein (Hsp) 60 involved anergic T cells that required exogenous IL-2 to proliferate. |
| 1529 | 10586096 | Responses to proinsulin, IA-2 (and tetanus toxoid) required no IL-2 and generated sufficient cytokine to rescue anergic T cell responses. |
| 1530 | 10593565 | To investigate whether GAD65 whole molecule, GAD65 p35 or insulin B chain peptide (amino acids 9-23) play an essential role in the pathogenesis of type 1 diabetes in the BioBreeding (BB) rat, we gave serial injections of GAD65, p35 or insulin B chain (9-23) to six groups of BB/Worcester rats. |
| 1531 | 10594551 | Autoantibodies to GAD, an important marker of the autoimmune process in type I or insulin-dependent diabetes mellitus (IDDM), are also found in non-diabetic individuals with autoimmune polyendocrine syndrome type 1 (APS1), APS2, and stiff man syndrome (SMS). |
| 1532 | 10594551 | Most IDDM sera contain two distinct GAD antibody specificities, one of which targets an epitope region in the middle-third of GAD65 (IDDM-E1; amino acids 221-359) and one of which targets the carboxy-third of GAD65 (IDDM-E2; amino acids 453-569). |
| 1533 | 10594551 | Using 11 chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of IgG antibodies from an individual with APS2-like disease (b35, b78, and b96) and MoAbs from an IDDM patient (MICA-2, MICA-3, and MICA-4). |
| 1534 | 10594551 | Neither the APS2 IgG antibodies nor the IDDM MoAbs bind the amino-terminal third of GAD65, but instead target the carboxy-terminal two-thirds of GAD65. |
| 1535 | 10594551 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in APS2 and IDDM. |
| 1536 | 10594551 | Autoantibodies to GAD, an important marker of the autoimmune process in type I or insulin-dependent diabetes mellitus (IDDM), are also found in non-diabetic individuals with autoimmune polyendocrine syndrome type 1 (APS1), APS2, and stiff man syndrome (SMS). |
| 1537 | 10594551 | Most IDDM sera contain two distinct GAD antibody specificities, one of which targets an epitope region in the middle-third of GAD65 (IDDM-E1; amino acids 221-359) and one of which targets the carboxy-third of GAD65 (IDDM-E2; amino acids 453-569). |
| 1538 | 10594551 | Using 11 chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of IgG antibodies from an individual with APS2-like disease (b35, b78, and b96) and MoAbs from an IDDM patient (MICA-2, MICA-3, and MICA-4). |
| 1539 | 10594551 | Neither the APS2 IgG antibodies nor the IDDM MoAbs bind the amino-terminal third of GAD65, but instead target the carboxy-terminal two-thirds of GAD65. |
| 1540 | 10594551 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in APS2 and IDDM. |
| 1541 | 10594551 | Autoantibodies to GAD, an important marker of the autoimmune process in type I or insulin-dependent diabetes mellitus (IDDM), are also found in non-diabetic individuals with autoimmune polyendocrine syndrome type 1 (APS1), APS2, and stiff man syndrome (SMS). |
| 1542 | 10594551 | Most IDDM sera contain two distinct GAD antibody specificities, one of which targets an epitope region in the middle-third of GAD65 (IDDM-E1; amino acids 221-359) and one of which targets the carboxy-third of GAD65 (IDDM-E2; amino acids 453-569). |
| 1543 | 10594551 | Using 11 chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of IgG antibodies from an individual with APS2-like disease (b35, b78, and b96) and MoAbs from an IDDM patient (MICA-2, MICA-3, and MICA-4). |
| 1544 | 10594551 | Neither the APS2 IgG antibodies nor the IDDM MoAbs bind the amino-terminal third of GAD65, but instead target the carboxy-terminal two-thirds of GAD65. |
| 1545 | 10594551 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in APS2 and IDDM. |
| 1546 | 10594551 | Autoantibodies to GAD, an important marker of the autoimmune process in type I or insulin-dependent diabetes mellitus (IDDM), are also found in non-diabetic individuals with autoimmune polyendocrine syndrome type 1 (APS1), APS2, and stiff man syndrome (SMS). |
| 1547 | 10594551 | Most IDDM sera contain two distinct GAD antibody specificities, one of which targets an epitope region in the middle-third of GAD65 (IDDM-E1; amino acids 221-359) and one of which targets the carboxy-third of GAD65 (IDDM-E2; amino acids 453-569). |
| 1548 | 10594551 | Using 11 chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of IgG antibodies from an individual with APS2-like disease (b35, b78, and b96) and MoAbs from an IDDM patient (MICA-2, MICA-3, and MICA-4). |
| 1549 | 10594551 | Neither the APS2 IgG antibodies nor the IDDM MoAbs bind the amino-terminal third of GAD65, but instead target the carboxy-terminal two-thirds of GAD65. |
| 1550 | 10594551 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in APS2 and IDDM. |
| 1551 | 10615947 | GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. |
| 1552 | 10615947 | Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). |
| 1553 | 10615947 | Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. |
| 1554 | 10615947 | Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. |
| 1555 | 10615947 | GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. |
| 1556 | 10615947 | Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). |
| 1557 | 10615947 | Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. |
| 1558 | 10615947 | Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. |
| 1559 | 10615947 | GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. |
| 1560 | 10615947 | Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). |
| 1561 | 10615947 | Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. |
| 1562 | 10615947 | Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. |
| 1563 | 10615947 | GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. |
| 1564 | 10615947 | Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). |
| 1565 | 10615947 | Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. |
| 1566 | 10615947 | Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. |
| 1567 | 10671565 | Two forms of glutamic-acid decarboxylase (GAD) have been identified in mammalian tissues: a 65-kDa form (GAD65) and a 67-kDa form (GAD67). |
| 1568 | 10672457 | Comments on the relation among GAD-65, IA-2 antibodies and body adiposity. |
| 1569 | 10814590 | Most insulin-dependent diabetes mellitus patients gen-erate conformational autoantibodies to the islet-cell 65-kDa variant of human glutamate decarboxylase (GAD65), and several immunochemical tests for the early detection of type-1 diabetes rely on GAD65 antibody (GADA) assessment using properly folded recombinant GAD65 as the antigen. |
| 1570 | 10814590 | However, this difficulty was recently surmounted in our laboratory by expressing GAD65 as a fusion protein with thioredoxin [Papouchado, Valdez, Ghiringhelli, Poskus and Ermácora (1997) Eur. |
| 1571 | 10814590 | The new gene was modified additionally to finally code for human GAD65 with a single amino-acid substitution: Met-161-->Thr. |
| 1572 | 10814590 | Also, a second 58-kDa by-product was identified as a GAD65 C-terminal proteolytic fragment that co-purifies with thioredoxin-M161T GAD65. |
| 1573 | 10814590 | Most insulin-dependent diabetes mellitus patients gen-erate conformational autoantibodies to the islet-cell 65-kDa variant of human glutamate decarboxylase (GAD65), and several immunochemical tests for the early detection of type-1 diabetes rely on GAD65 antibody (GADA) assessment using properly folded recombinant GAD65 as the antigen. |
| 1574 | 10814590 | However, this difficulty was recently surmounted in our laboratory by expressing GAD65 as a fusion protein with thioredoxin [Papouchado, Valdez, Ghiringhelli, Poskus and Ermácora (1997) Eur. |
| 1575 | 10814590 | The new gene was modified additionally to finally code for human GAD65 with a single amino-acid substitution: Met-161-->Thr. |
| 1576 | 10814590 | Also, a second 58-kDa by-product was identified as a GAD65 C-terminal proteolytic fragment that co-purifies with thioredoxin-M161T GAD65. |
| 1577 | 10814590 | Most insulin-dependent diabetes mellitus patients gen-erate conformational autoantibodies to the islet-cell 65-kDa variant of human glutamate decarboxylase (GAD65), and several immunochemical tests for the early detection of type-1 diabetes rely on GAD65 antibody (GADA) assessment using properly folded recombinant GAD65 as the antigen. |
| 1578 | 10814590 | However, this difficulty was recently surmounted in our laboratory by expressing GAD65 as a fusion protein with thioredoxin [Papouchado, Valdez, Ghiringhelli, Poskus and Ermácora (1997) Eur. |
| 1579 | 10814590 | The new gene was modified additionally to finally code for human GAD65 with a single amino-acid substitution: Met-161-->Thr. |
| 1580 | 10814590 | Also, a second 58-kDa by-product was identified as a GAD65 C-terminal proteolytic fragment that co-purifies with thioredoxin-M161T GAD65. |
| 1581 | 10814590 | Most insulin-dependent diabetes mellitus patients gen-erate conformational autoantibodies to the islet-cell 65-kDa variant of human glutamate decarboxylase (GAD65), and several immunochemical tests for the early detection of type-1 diabetes rely on GAD65 antibody (GADA) assessment using properly folded recombinant GAD65 as the antigen. |
| 1582 | 10814590 | However, this difficulty was recently surmounted in our laboratory by expressing GAD65 as a fusion protein with thioredoxin [Papouchado, Valdez, Ghiringhelli, Poskus and Ermácora (1997) Eur. |
| 1583 | 10814590 | The new gene was modified additionally to finally code for human GAD65 with a single amino-acid substitution: Met-161-->Thr. |
| 1584 | 10814590 | Also, a second 58-kDa by-product was identified as a GAD65 C-terminal proteolytic fragment that co-purifies with thioredoxin-M161T GAD65. |
| 1585 | 10824708 | Newly diagnosed latent autoimmune diabetes in adults (LADA) is associated with low level glutamate decarboxylase (GAD65) and IA-2 autoantibodies. |
| 1586 | 10862868 | We have created a hybrid form of GAD consisting of amino acids 1-101 of the human GAD67 protein fused to amino acids 96-585 of the human GAD65 protein, and have modified this to include a C-terminal hexa-Histidine (H6) tag sequence. |
| 1587 | 10862868 | This hybrid GAD67/65-H6 was expressed in two yeast hosts: constitutively under the control of the plasmid phosphoglycerate kinase promoter (PGK1) in Saccharomyces cerevisiae, and inducibly under the control of the chromosomal alcohol oxidase promoter (AOX1) in Pichia pastoris. |
| 1588 | 10868836 | Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality. |
| 1589 | 10909282 | Antibodies recognising different pancreatic autoantigens (Abs) are detected many years before the clinical onset of insulin-dependent diabetes mellitus (IDDM). |
| 1590 | 10909282 | The aim of the study was the estimation of the prevalence and titre of the antibodies directed against protein tyrosine phosphatase-2 (IA-2) and glutamic acid decarboxylase (GAD) in patients with newly diagnosed diabetes type 1 and their first degree relatives. |
| 1591 | 10909282 | IA-2A and GADA were performed by radiobinding assay (RIA) using 2 microliters of serum and recombinant S35-labelled GAD65 and IA-2 antigens. |
| 1592 | 10912505 | Insulin-dependent diabetes mellitus (IDDM) develops in nonobese diabetic (NOD) mice through the destruction of the B cells in pancreatic Langerhans islets by islet autoantigen-specific T cells. |
| 1593 | 10912505 | The islet autoantigen glutamic acid decarboxylase 65 (GAD65) is thought to be a major target autoantigen in IDDM. |
| 1594 | 10939716 | The detection of such autoantibodies in patients with small-cell lung carcinoma (SCLC) without LEMS suggests that these autoantigens, GAD65 and IA-2, could be produced by SCLC tissue. |
| 1595 | 10984128 | GAD65 autoantibodies are also present in a subset of patients with type 2 diabetes who frequently become insulin dependent. |
| 1596 | 10999825 | We studied the association between glutamic acid decarboxylase (GAD65) and islet cell (IA-2) autoantibodies as well as autoantibodies to the autonomic nervous system and peripheral nerve function in recent onset type 1 diabetes. |
| 1597 | 11033022 | The format worked well using diverse antigens such as 35S-met-GAD65, 35S-met-ICA512/IA2, 35S-met-Phogrin, and 125I-insulin, and could be used for simultaneous screening of reactivity to both GAD65 and ICA512/IA2 in the same well. |
| 1598 | 11033022 | Diagnostic accuracy compared favorably with microcentrifuge tube-based Protein A-agarose GAD65 and IA2 autoantibody radiobinding assays and with acid-charcoal-polyethylene glycol (PEG) based competitive insulin autoantibody assays. |
| 1599 | 11033022 | Total serum volumes required were only 6 microl for GAD and ICA512, and only 15 microl for IAA. |
| 1600 | 11033022 | The format worked well using diverse antigens such as 35S-met-GAD65, 35S-met-ICA512/IA2, 35S-met-Phogrin, and 125I-insulin, and could be used for simultaneous screening of reactivity to both GAD65 and ICA512/IA2 in the same well. |
| 1601 | 11033022 | Diagnostic accuracy compared favorably with microcentrifuge tube-based Protein A-agarose GAD65 and IA2 autoantibody radiobinding assays and with acid-charcoal-polyethylene glycol (PEG) based competitive insulin autoantibody assays. |
| 1602 | 11033022 | Total serum volumes required were only 6 microl for GAD and ICA512, and only 15 microl for IAA. |
| 1603 | 11049787 | The patient did not develop antibodies to GAD(65) either. |
| 1604 | 11049787 | Absence of evidence for direct cytolytic action or an indirect effect through molecular mimicry with GAD(65) in the present case raises the possibility of another indirect pathway through which enteroviruses can cause diabetes mellitus. |
| 1605 | 11049787 | The patient did not develop antibodies to GAD(65) either. |
| 1606 | 11049787 | Absence of evidence for direct cytolytic action or an indirect effect through molecular mimicry with GAD(65) in the present case raises the possibility of another indirect pathway through which enteroviruses can cause diabetes mellitus. |
| 1607 | 11106928 | In addition, the T cell activation markers HLA-DR, IL-2 receptor and transferrin receptor) were not upregulated. |
| 1608 | 11106928 | Anti-glutamate decarboxylase (GAD65) and anti-IA-2 antibodies remained persistently high. |
| 1609 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1610 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1611 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1612 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1613 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1614 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1615 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1616 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1617 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1618 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1619 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1620 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1621 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1622 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1623 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1624 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1625 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1626 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1627 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1628 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1629 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1630 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1631 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1632 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1633 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1634 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1635 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1636 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1637 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1638 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1639 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1640 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1641 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1642 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1643 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1644 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1645 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1646 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1647 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1648 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1649 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1650 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1651 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1652 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1653 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1654 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1655 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1656 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1657 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1658 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1659 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1660 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1661 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1662 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1663 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1664 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1665 | 11121550 | Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2. |
| 1666 | 11121550 | Assays to detect autoantibodies to glutamic acid decarboxylase (GAD65) and the protein tyrosine phosphatase-like molecule IA-2, which are both present in pancreatic islets, have been used in the diagnosis and prediction of type 1 diabetes. |
| 1667 | 11121550 | In this study a novel fusion protein combining the entire GAD65 molecule with the 40 kDa intracellular domain of IA-2 (GAD-IA-2) was constructed to detect autoantibodies to both antigens by one single assay. |
| 1668 | 11121550 | For the same purpose a truncated version of this fusion protein which contained the entire GAD65 linked to the 203 carboxy-terminal amino acids of IA-2 (GAD-dIA-2) was made. |
| 1669 | 11121550 | A panel of 34 diabetic sera which represented unequivocally positive or negative antibody responses to GAD65 and/or IA-2 as well as 20 serum samples from healthy controls were tested in a radioligand binding assay with the constructed fusion proteins as antigens. |
| 1670 | 11121550 | Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2. |
| 1671 | 11121550 | The full-length, as well as the truncated fusion protein detected all samples positive for antibodies either to GAD65 or IA-2 or both, except for one GAD65 antibody positive sample. |
| 1672 | 11121550 | We conclude that the principle of a combinatorial molecule where a fusion protein expresses both GAD65 and IA-2 epitopes is feasible, and such a fusion protein can be used instead of the single antigens to reduce time and costs of large-scale screening for clinical purposes. |
| 1673 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1674 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1675 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1676 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1677 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1678 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1679 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1680 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1681 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1682 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1683 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1684 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1685 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1686 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1687 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1688 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1689 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1690 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1691 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1692 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1693 | 11172025 | We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. |
| 1694 | 11172025 | Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. |
| 1695 | 11172025 | This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM. |
| 1696 | 11172025 | We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. |
| 1697 | 11172025 | Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. |
| 1698 | 11172025 | This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM. |
| 1699 | 11172025 | We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. |
| 1700 | 11172025 | Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. |
| 1701 | 11172025 | This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM. |
| 1702 | 11192752 | [Autoantibodies to GAD65, IA2 and insulin in Czech children with type 1 diabetes]. |
| 1703 | 11207247 | CD4(+) T cells arise spontaneously in young NOD mice to an apparently dominant determinant found within the GAD65 peptide 530--543 (p530); however, T cells to the overlapping determinant 524-538 (p524) dominate the response only after immunization with GAD65(524--543). |
| 1704 | 11207247 | T cell clones and hybridomas from both of these T cell groups were responsive to APC pulsed with GAD65(524--543) or whole rGAD65. p524-reactive cells appeared to be regulatory upon adoptive transfer into young NOD mice and could inhibit insulin-dependent diabetes mellitus development, although they were unable to produce IL-4, IL-10, or TGF beta upon antigenic challenge. |
| 1705 | 11207247 | CD4(+) T cells arise spontaneously in young NOD mice to an apparently dominant determinant found within the GAD65 peptide 530--543 (p530); however, T cells to the overlapping determinant 524-538 (p524) dominate the response only after immunization with GAD65(524--543). |
| 1706 | 11207247 | T cell clones and hybridomas from both of these T cell groups were responsive to APC pulsed with GAD65(524--543) or whole rGAD65. p524-reactive cells appeared to be regulatory upon adoptive transfer into young NOD mice and could inhibit insulin-dependent diabetes mellitus development, although they were unable to produce IL-4, IL-10, or TGF beta upon antigenic challenge. |
| 1707 | 11274421 | We screened synthetic peptide libraries dedicated to bind to HLA-DR3, which predisposes to both diseases, using clonal CD4(+) T cells reactive to GAD65 isolated from a prediabetic stiff-man syndrome patient. |
| 1708 | 11359854 | Several studies have provided indirect evidence in support of a role for beta cell-specific Th2 cells in regulating insulin-dependent diabetes (IDDM). |
| 1709 | 11359854 | Adoptive transfer of a GAD65-specific Th2 cell clone (characterized by the secretion of IL-4, IL-5, and IL-10, but not IFN-gamma or TGF-beta) into 2- or 12-wk-old NOD female recipients prevented the progression of insulitis and subsequent development of overt IDDM. |
| 1710 | 11359854 | The immunoregulatory function of a given Th cell clone was dependent on the relative levels of IFN-gamma vs IL-4 and IL-10 secreted. |
| 1711 | 11378213 | We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5+/-6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD(65) and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. |
| 1712 | 11378213 | A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD(65) plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. |
| 1713 | 11378213 | However, GAD(65) antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. |
| 1714 | 11378213 | The fibrocalculous pancreatopathy group showed GAD(65) plus IA-2 autoantibody positivity in 14.2% and GAD(65) autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. |
| 1715 | 11378213 | We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5+/-6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD(65) and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. |
| 1716 | 11378213 | A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD(65) plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. |
| 1717 | 11378213 | However, GAD(65) antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. |
| 1718 | 11378213 | The fibrocalculous pancreatopathy group showed GAD(65) plus IA-2 autoantibody positivity in 14.2% and GAD(65) autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. |
| 1719 | 11378213 | We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5+/-6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD(65) and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. |
| 1720 | 11378213 | A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD(65) plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. |
| 1721 | 11378213 | However, GAD(65) antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. |
| 1722 | 11378213 | The fibrocalculous pancreatopathy group showed GAD(65) plus IA-2 autoantibody positivity in 14.2% and GAD(65) autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. |
| 1723 | 11378213 | We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5+/-6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD(65) and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. |
| 1724 | 11378213 | A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD(65) plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. |
| 1725 | 11378213 | However, GAD(65) antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. |
| 1726 | 11378213 | The fibrocalculous pancreatopathy group showed GAD(65) plus IA-2 autoantibody positivity in 14.2% and GAD(65) autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. |
| 1727 | 11409713 | Regions of homology exist between GAD65 (residues 250-273) and the Coxsackie P2-C protein (residues 28-50) and between GAD65 (residues 506-518) and proinsulin (residues 24-36), and each of these has been reported to be a diabetes-associated T cell target. |
| 1728 | 11409713 | These data suggest that proliferative T cell responses to peptides containing putative autoreactive epitopes of GAD65 and proinsulin are not specific for type 1 diabetes, that correlation between T cell reactivity to peptides is not restricted to those containing homologous regions, and that non-antigen-specific factors are important determinants of in vitro measurements of T cell reactivity. |
| 1729 | 11409713 | Regions of homology exist between GAD65 (residues 250-273) and the Coxsackie P2-C protein (residues 28-50) and between GAD65 (residues 506-518) and proinsulin (residues 24-36), and each of these has been reported to be a diabetes-associated T cell target. |
| 1730 | 11409713 | These data suggest that proliferative T cell responses to peptides containing putative autoreactive epitopes of GAD65 and proinsulin are not specific for type 1 diabetes, that correlation between T cell reactivity to peptides is not restricted to those containing homologous regions, and that non-antigen-specific factors are important determinants of in vitro measurements of T cell reactivity. |
| 1731 | 11414702 | Utilizing this library, we isolated a cross-reactive epitope recognized by a glutamic acid decarboxylase (GAD) 65-autoreactive T cell clone established from a patient with insulin-dependent diabetes mellitus. |
| 1732 | 11414702 | Although the newly identified epitope (PVQLSNQWHVVGATF) was far different from the original epitope, GAD65 p116-128 (NILLQYVVKSFDR), it did have the capacity to stimulate the T cell clone comparable to that of the original GAD epitope. |
| 1733 | 11416235 | Influence of sex and age at onset on autoantibodies against insulin, GAD65 and IA2 in recent onset type 1 diabetic patients. |
| 1734 | 11418696 | Initial studies indicated that exposure to glutamic acid decarboxylase (GAD65) peptides in utero resulted in delay or transient protection from insulin-dependent diabetes mellitus (IDDM) in NOD mice. |
| 1735 | 11418696 | To more closely examine the effects of early and late exposure to diabetogenic Ags on T cells, we applied peptides derived from GAD65 (GAD AA 246-266, 509-528, and 524-543), to our "in vitro IDDM" (ivIDDM) model. |
| 1736 | 11418696 | T cells derived from NOD FTOC primed during the latter stages of organ culture, when mature T cell phenotypes are present, had the ability to proliferate to GAD peptides. ivIDDM was exacerbated under these conditions, suggesting that GAD responsiveness correlates with the ivIDDM phenotype, and parallels the acceleration of IDDM we had seen in young adult NOD mice. |
| 1737 | 11418696 | Initial studies indicated that exposure to glutamic acid decarboxylase (GAD65) peptides in utero resulted in delay or transient protection from insulin-dependent diabetes mellitus (IDDM) in NOD mice. |
| 1738 | 11418696 | To more closely examine the effects of early and late exposure to diabetogenic Ags on T cells, we applied peptides derived from GAD65 (GAD AA 246-266, 509-528, and 524-543), to our "in vitro IDDM" (ivIDDM) model. |
| 1739 | 11418696 | T cells derived from NOD FTOC primed during the latter stages of organ culture, when mature T cell phenotypes are present, had the ability to proliferate to GAD peptides. ivIDDM was exacerbated under these conditions, suggesting that GAD responsiveness correlates with the ivIDDM phenotype, and parallels the acceleration of IDDM we had seen in young adult NOD mice. |
| 1740 | 11418698 | We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 1741 | 11418698 | Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. |
| 1742 | 11418698 | Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. |
| 1743 | 11418698 | Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. |
| 1744 | 11418698 | In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. |
| 1745 | 11418698 | Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. |
| 1746 | 11418698 | These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM. |
| 1747 | 11418698 | We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 1748 | 11418698 | Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. |
| 1749 | 11418698 | Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. |
| 1750 | 11418698 | Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. |
| 1751 | 11418698 | In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. |
| 1752 | 11418698 | Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. |
| 1753 | 11418698 | These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM. |
| 1754 | 11466400 | CD4(+) T cell responses to glutamic acid decarboxylase (GAD65) spontaneously arise in nonobese diabetic (NOD) mice before the onset of insulin-dependent diabetes mellitus (IDDM) and may be critical to the pathogenic process. |
| 1755 | 11466400 | However, since both CD4(+) and CD8(+) T cells are involved in autoimmune diabetes, we sought to determine whether GAD65-specific CD8(+) T cells were also present in prediabetic NOD mice and contribute to IDDM. |
| 1756 | 11466400 | Naive NOD spleen cells stimulated with GAD65 peptides 206-214 (p206) and 546-554 (p546) produced IFN-gamma and showed Ag-specific CTL responses against targets pulsed with homologous peptide. |
| 1757 | 11466400 | Spontaneous CTL responses to p206 and p546 were mediated by CD8(+) T cells that are capable of lysing GAD65-expressing target cells, and p546-specific T cells transferred insulitis to NOD.scid mice. |
| 1758 | 11466400 | This report reveals a potential therapeutic role for MHC class I-restricted peptides in treating autoimmune disease and revisits the notion that the CD4- and CD8-inducing determinants on some molecules may benefit from a proximal relationship. |
| 1759 | 11466400 | CD4(+) T cell responses to glutamic acid decarboxylase (GAD65) spontaneously arise in nonobese diabetic (NOD) mice before the onset of insulin-dependent diabetes mellitus (IDDM) and may be critical to the pathogenic process. |
| 1760 | 11466400 | However, since both CD4(+) and CD8(+) T cells are involved in autoimmune diabetes, we sought to determine whether GAD65-specific CD8(+) T cells were also present in prediabetic NOD mice and contribute to IDDM. |
| 1761 | 11466400 | Naive NOD spleen cells stimulated with GAD65 peptides 206-214 (p206) and 546-554 (p546) produced IFN-gamma and showed Ag-specific CTL responses against targets pulsed with homologous peptide. |
| 1762 | 11466400 | Spontaneous CTL responses to p206 and p546 were mediated by CD8(+) T cells that are capable of lysing GAD65-expressing target cells, and p546-specific T cells transferred insulitis to NOD.scid mice. |
| 1763 | 11466400 | This report reveals a potential therapeutic role for MHC class I-restricted peptides in treating autoimmune disease and revisits the notion that the CD4- and CD8-inducing determinants on some molecules may benefit from a proximal relationship. |
| 1764 | 11466400 | CD4(+) T cell responses to glutamic acid decarboxylase (GAD65) spontaneously arise in nonobese diabetic (NOD) mice before the onset of insulin-dependent diabetes mellitus (IDDM) and may be critical to the pathogenic process. |
| 1765 | 11466400 | However, since both CD4(+) and CD8(+) T cells are involved in autoimmune diabetes, we sought to determine whether GAD65-specific CD8(+) T cells were also present in prediabetic NOD mice and contribute to IDDM. |
| 1766 | 11466400 | Naive NOD spleen cells stimulated with GAD65 peptides 206-214 (p206) and 546-554 (p546) produced IFN-gamma and showed Ag-specific CTL responses against targets pulsed with homologous peptide. |
| 1767 | 11466400 | Spontaneous CTL responses to p206 and p546 were mediated by CD8(+) T cells that are capable of lysing GAD65-expressing target cells, and p546-specific T cells transferred insulitis to NOD.scid mice. |
| 1768 | 11466400 | This report reveals a potential therapeutic role for MHC class I-restricted peptides in treating autoimmune disease and revisits the notion that the CD4- and CD8-inducing determinants on some molecules may benefit from a proximal relationship. |
| 1769 | 11466400 | CD4(+) T cell responses to glutamic acid decarboxylase (GAD65) spontaneously arise in nonobese diabetic (NOD) mice before the onset of insulin-dependent diabetes mellitus (IDDM) and may be critical to the pathogenic process. |
| 1770 | 11466400 | However, since both CD4(+) and CD8(+) T cells are involved in autoimmune diabetes, we sought to determine whether GAD65-specific CD8(+) T cells were also present in prediabetic NOD mice and contribute to IDDM. |
| 1771 | 11466400 | Naive NOD spleen cells stimulated with GAD65 peptides 206-214 (p206) and 546-554 (p546) produced IFN-gamma and showed Ag-specific CTL responses against targets pulsed with homologous peptide. |
| 1772 | 11466400 | Spontaneous CTL responses to p206 and p546 were mediated by CD8(+) T cells that are capable of lysing GAD65-expressing target cells, and p546-specific T cells transferred insulitis to NOD.scid mice. |
| 1773 | 11466400 | This report reveals a potential therapeutic role for MHC class I-restricted peptides in treating autoimmune disease and revisits the notion that the CD4- and CD8-inducing determinants on some molecules may benefit from a proximal relationship. |
| 1774 | 11473034 | Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive T-cells in type 1 diabetes: report of phase II of the Second International Immunology of Diabetes Society Workshop for Standardization of T-cell assays in type 1 diabetes. |
| 1775 | 11473034 | The identification, quantification, and characterization of T-cells reactive with the islet autoantigens GAD65, proinsulin (PI), and tyrosine phosphatase-like molecules IA-2 and phogrin are major research goals in type 1 diabetes. |
| 1776 | 11473034 | Through this process, we have been able to identify preparations of GAD65 and IA-2, generated in insect cells using the baculovirus expression system, that stimulate relevant clones and display low inhibitory effects on third-party antigens. |
| 1777 | 11473034 | Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive T-cells in type 1 diabetes: report of phase II of the Second International Immunology of Diabetes Society Workshop for Standardization of T-cell assays in type 1 diabetes. |
| 1778 | 11473034 | The identification, quantification, and characterization of T-cells reactive with the islet autoantigens GAD65, proinsulin (PI), and tyrosine phosphatase-like molecules IA-2 and phogrin are major research goals in type 1 diabetes. |
| 1779 | 11473034 | Through this process, we have been able to identify preparations of GAD65 and IA-2, generated in insect cells using the baculovirus expression system, that stimulate relevant clones and display low inhibitory effects on third-party antigens. |
| 1780 | 11473034 | Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive T-cells in type 1 diabetes: report of phase II of the Second International Immunology of Diabetes Society Workshop for Standardization of T-cell assays in type 1 diabetes. |
| 1781 | 11473034 | The identification, quantification, and characterization of T-cells reactive with the islet autoantigens GAD65, proinsulin (PI), and tyrosine phosphatase-like molecules IA-2 and phogrin are major research goals in type 1 diabetes. |
| 1782 | 11473034 | Through this process, we have been able to identify preparations of GAD65 and IA-2, generated in insect cells using the baculovirus expression system, that stimulate relevant clones and display low inhibitory effects on third-party antigens. |
| 1783 | 11487177 | To estimate the regional difference in the degree of association between these autoantibodies, autoantibodies reacting with ICA512/IA-2 (ICA512) and GAD65 in addition to ICA were analyzed in 131 Korean children with type 1 diabetes. |
| 1784 | 11532327 | Higher prevalence of GAD antibody in diabetes patients using a new radioligand-binding assay with recombinant human GAD65 antibodies (GAD65Ab) has been seen in several studies. |
| 1785 | 11532327 | There was no significant difference in gender, diabetes onset and duration, HbA1c, C-peptide concentration and frequencies of HLA DR3, DR4, DR9, DR3/DR4, DR3/DR9 and DR4/DR9 genotypes between GAD65Ab+ and GAD65Ab- groups. |
| 1786 | 11532327 | The frequencies of antimicrosomal and anti-thyroglobulin antibodies in GAD65Ab+ (13.5,8.1%, respectively) were not different from GAD65- patients (9.4,12.5%, respectively). |
| 1787 | 11532327 | Higher prevalence of GAD antibody in diabetes patients using a new radioligand-binding assay with recombinant human GAD65 antibodies (GAD65Ab) has been seen in several studies. |
| 1788 | 11532327 | There was no significant difference in gender, diabetes onset and duration, HbA1c, C-peptide concentration and frequencies of HLA DR3, DR4, DR9, DR3/DR4, DR3/DR9 and DR4/DR9 genotypes between GAD65Ab+ and GAD65Ab- groups. |
| 1789 | 11532327 | The frequencies of antimicrosomal and anti-thyroglobulin antibodies in GAD65Ab+ (13.5,8.1%, respectively) were not different from GAD65- patients (9.4,12.5%, respectively). |
| 1790 | 11561476 | To this end, 20 children (8 males, 12 females), ages 1-15 years, admitted to the University Pediatric Hospital with type 1 diabetes de novo between November 2000 and April 2001 were prospectively studied to determine the presence of serum antibodies against Islet cells (ICA), glutamic acid decarboxylase (GAD-65) and insulin autoantibodies (IAA). |
| 1791 | 11585368 | Autoantibodies to IA-2 and GAD65 in patients with type 2 diabetes mellitus of varied duration: prevalence and correlation with clinical features. |
| 1792 | 11591120 | In comparison with IRF-1(+/+), the percentage of CD4(+) and Mac-1(+) splenic cells significantly increased, whereas CD3(+), CD8(+) and B220(+) cells decreased in IRF-1(-/-). |
| 1793 | 11591120 | Furthermore, spleen cell proliferation in response to Con A or murine GAD65 peptide, a major autoantigen of the pancreatic beta-cell, significantly increased, and the IFN-gamma/IL-10 ratio in the culture supernatant significantly decreased in IRF-1(-/-), suggesting Th2 deviation in cytokine balance. |
| 1794 | 11600569 | Islet cell antibody (ICA), insulin autoantibody, glutamic acid decarboxylase (GAD(65)), and protein tyrosine phosphatase autoantibodies were measured and human leucocyte antigen (HLA) class II alleles DRB1 and DQB1 genotyping was performed. |
| 1795 | 11600569 | A subgroup of 26 probands (12 ICA+, 14 ICA-) was tested for GAD(65) and was found positive. 4/14 ICA+ first-degree relatives were GAD(65) positive. |
| 1796 | 11600569 | HLA-DRB1 was found to be associated with the presence of ICA in both probands and relatives, whereas HLA-DPB1 was associated with autoantibody in relatives of type 1 diabetic probands. |
| 1797 | 11606180 | Comparison of autoantibodies to IA-2 and GAD65 in the rapid- and the slow-onset, adult Type 1 diabetes in Thailand. |
| 1798 | 11673498 | Peripheral T cells reactive to the insulin, glutamic acid decarboxylase 65 (GAD65), GAD67, and islet cell Ag p69 autoantigens were also detected in these mice, indicating that NOD mice are not tolerant to any of these islet autoantigens at this young age. |
| 1799 | 11681492 | Balance of GAD65-specific IL-10 production and polyclonal Th1-type response in type 1 diabetes. |
| 1800 | 11681492 | In this study, higher glutamic acid decarboxylase 65 (GAD65)-specific IL-10 production was observed at 10-12 weeks in NOD mice, and a marked increase of Th1-type response (IFN-gamma production) upon polyclonal (anti-CD3 antibody) stimulation was observed just before diabetes development along with a decline of GAD65-specific IL-10 production. |
| 1801 | 11681492 | Moreover, there was a clear negative correlation between IL-10 level upon GAD65 stimulation and log(IFN-gamma) level upon anti-CD3 antibody stimulation (r=-0.999, p<0.001). |
| 1802 | 11681492 | These results suggest that the balance between GAD65-specific IL-10 production and polyclonal Th1-type response may regulate the onset of hyperglycemia in type 1 diabetes in NOD mice. |
| 1803 | 11681492 | Balance of GAD65-specific IL-10 production and polyclonal Th1-type response in type 1 diabetes. |
| 1804 | 11681492 | In this study, higher glutamic acid decarboxylase 65 (GAD65)-specific IL-10 production was observed at 10-12 weeks in NOD mice, and a marked increase of Th1-type response (IFN-gamma production) upon polyclonal (anti-CD3 antibody) stimulation was observed just before diabetes development along with a decline of GAD65-specific IL-10 production. |
| 1805 | 11681492 | Moreover, there was a clear negative correlation between IL-10 level upon GAD65 stimulation and log(IFN-gamma) level upon anti-CD3 antibody stimulation (r=-0.999, p<0.001). |
| 1806 | 11681492 | These results suggest that the balance between GAD65-specific IL-10 production and polyclonal Th1-type response may regulate the onset of hyperglycemia in type 1 diabetes in NOD mice. |
| 1807 | 11681492 | Balance of GAD65-specific IL-10 production and polyclonal Th1-type response in type 1 diabetes. |
| 1808 | 11681492 | In this study, higher glutamic acid decarboxylase 65 (GAD65)-specific IL-10 production was observed at 10-12 weeks in NOD mice, and a marked increase of Th1-type response (IFN-gamma production) upon polyclonal (anti-CD3 antibody) stimulation was observed just before diabetes development along with a decline of GAD65-specific IL-10 production. |
| 1809 | 11681492 | Moreover, there was a clear negative correlation between IL-10 level upon GAD65 stimulation and log(IFN-gamma) level upon anti-CD3 antibody stimulation (r=-0.999, p<0.001). |
| 1810 | 11681492 | These results suggest that the balance between GAD65-specific IL-10 production and polyclonal Th1-type response may regulate the onset of hyperglycemia in type 1 diabetes in NOD mice. |
| 1811 | 11681492 | Balance of GAD65-specific IL-10 production and polyclonal Th1-type response in type 1 diabetes. |
| 1812 | 11681492 | In this study, higher glutamic acid decarboxylase 65 (GAD65)-specific IL-10 production was observed at 10-12 weeks in NOD mice, and a marked increase of Th1-type response (IFN-gamma production) upon polyclonal (anti-CD3 antibody) stimulation was observed just before diabetes development along with a decline of GAD65-specific IL-10 production. |
| 1813 | 11681492 | Moreover, there was a clear negative correlation between IL-10 level upon GAD65 stimulation and log(IFN-gamma) level upon anti-CD3 antibody stimulation (r=-0.999, p<0.001). |
| 1814 | 11681492 | These results suggest that the balance between GAD65-specific IL-10 production and polyclonal Th1-type response may regulate the onset of hyperglycemia in type 1 diabetes in NOD mice. |
| 1815 | 11681491 | Recent studies have described linkage and association of type 1 diabetes to the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene (IDDM12)in Caucasians. |
| 1816 | 11681491 | We also investigated association between this CTLA-4 gene polymorphism and GAD65 antibody positivity in 103 of the patients. |
| 1817 | 11681491 | There was no significant difference in the distribution of CTLA-4 alleles between patients and controls, and no difference was observed in the prevalence of CTLA-4 alleles when GAD65 antibody-positive and -negative individuals with the type 1 diabetes were compared. |
| 1818 | 11681491 | Recent studies have described linkage and association of type 1 diabetes to the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene (IDDM12)in Caucasians. |
| 1819 | 11681491 | We also investigated association between this CTLA-4 gene polymorphism and GAD65 antibody positivity in 103 of the patients. |
| 1820 | 11681491 | There was no significant difference in the distribution of CTLA-4 alleles between patients and controls, and no difference was observed in the prevalence of CTLA-4 alleles when GAD65 antibody-positive and -negative individuals with the type 1 diabetes were compared. |
| 1821 | 11822582 | The criteria for type 2 DM were absent islet cell (IA-2) and glutamic acid decarboxylase (GAD65) antibodies and a fasting serum C-peptide level of > or = 0.23 nmol/l. |
| 1822 | 11879720 | GAD65 and IA-2 autoantibodies are common in a subset of siblings of Sardinian Type 2 diabetes families. |
| 1823 | 11905849 | Complexity of human immune response profiles for CD4+ T cell epitopes from the diabetes autoantigen GAD65. |
| 1824 | 11905849 | We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplotypes characteristic of susceptibility to IDDM. |
| 1825 | 11905849 | The majority of T cell responses were restricted by DRB1 molecules; however, DRB4 restricted responses were also observed. |
| 1826 | 11905849 | Complexity of human immune response profiles for CD4+ T cell epitopes from the diabetes autoantigen GAD65. |
| 1827 | 11905849 | We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplotypes characteristic of susceptibility to IDDM. |
| 1828 | 11905849 | The majority of T cell responses were restricted by DRB1 molecules; however, DRB4 restricted responses were also observed. |
| 1829 | 11927616 | We found that in patients with new-onset type 1 diabetes, GAD65-reactive T cells were strikingly less dependent on CD28 and B7-1 costimulation to enter into cell cycle and proliferate than were equivalent cells derived from healthy controls. |
| 1830 | 11927616 | In addition, we observed different effects with selective blockade of either B7-1 or B7-2 molecules; B7-1 appears to deliver a negative signal by engaging CTLA-4, while B7-2 engagement of CD28 upregulates T cell proliferation and cytokine secretion. |
| 1831 | 11978629 | Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. |
| 1832 | 12021093 | Antibodies (Abs) to tyrosine pyrophosphatase (IA2-Abs), glutamate decarboxylase 65 (GAD65-Abs), and other minor markers like ICA12 Abs and tissue transglutaminase Abs (TTG-Abs) were studied. |
| 1833 | 12021093 | Of the MMDM patients 30% were positive for either GAD65 or IA-2 antibodies, and 14% were positive for ICA12 antibodies. |
| 1834 | 12021103 | A human-derived monoclonal antibody (mAb) MICA3 reacts with a surface loop of GAD65 that includes PEVKEK, and mutagenic deletion of this loop was shown to reduce reactivity of GAD with the mAb by 70%. |
| 1835 | 12021103 | To establish that the PEVKEK motif on GAD65 contains a major epitope for diabetes sera and to identify the amino acids involved, mutants of nucleotides of GAD65 and GAD67 at sites in the PEVKEK motif were created and the expressed proteins used for radioimmunoprecipitation (RIP) tests with sera from patients with type 1 diabetes. |
| 1836 | 12021103 | A human-derived monoclonal antibody (mAb) MICA3 reacts with a surface loop of GAD65 that includes PEVKEK, and mutagenic deletion of this loop was shown to reduce reactivity of GAD with the mAb by 70%. |
| 1837 | 12021103 | To establish that the PEVKEK motif on GAD65 contains a major epitope for diabetes sera and to identify the amino acids involved, mutants of nucleotides of GAD65 and GAD67 at sites in the PEVKEK motif were created and the expressed proteins used for radioimmunoprecipitation (RIP) tests with sera from patients with type 1 diabetes. |
| 1838 | 12021109 | This study attempts to assess the prevalence of various autoantibodies in early-onset diabetics in northern India, with emphasis on antibodies against glutamic acid decarboxylase (GAD65), IA-2, ICA-12, 21-hydroxylase (21-OH), and tissue transglutaminase (TTG). |
| 1839 | 12021109 | GAD65 and IA-2 antibodies were found to be present in approximately 26% of cases of type 1 diabetes. |
| 1840 | 12021109 | This study attempts to assess the prevalence of various autoantibodies in early-onset diabetics in northern India, with emphasis on antibodies against glutamic acid decarboxylase (GAD65), IA-2, ICA-12, 21-hydroxylase (21-OH), and tissue transglutaminase (TTG). |
| 1841 | 12021109 | GAD65 and IA-2 antibodies were found to be present in approximately 26% of cases of type 1 diabetes. |
| 1842 | 12021112 | We examined the frequencies of autoantibodies to glutamate decarboxylase, GAD65, protein tyrosine phosphatase, IA-2/ICA512, and insulin, and of HLA class II markers in ICA-positive first-degree relatives of patients with type 1 diabetes. |
| 1843 | 12021116 | GAD65 and ICA512 antibodies in undernourished and normally nourished south Indian patients with diabetes. |
| 1844 | 12021116 | The frequency of GAD65 and ICA512 antibodies in Indian IDDM patients is similar to that in Caucasians. |
| 1845 | 12021116 | The prevalence of GAD65 and ICA512 autoantibodies in controls from south India was 4% and 2%, respectively. |
| 1846 | 12021116 | One hundred thirty-one diabetic patients (undernourished [UNDM], n = 67; and normal nourished [NNDM], n = 64) were assayed for GAD65 and ICA512 autoantibodies. |
| 1847 | 12021116 | The results suggest that GAD65 and ICA512 antibody frequencies are neither significantly increased nor decreased in UNDM patients compared to NNDM patients. |
| 1848 | 12021116 | GAD65 and ICA512 antibodies in undernourished and normally nourished south Indian patients with diabetes. |
| 1849 | 12021116 | The frequency of GAD65 and ICA512 antibodies in Indian IDDM patients is similar to that in Caucasians. |
| 1850 | 12021116 | The prevalence of GAD65 and ICA512 autoantibodies in controls from south India was 4% and 2%, respectively. |
| 1851 | 12021116 | One hundred thirty-one diabetic patients (undernourished [UNDM], n = 67; and normal nourished [NNDM], n = 64) were assayed for GAD65 and ICA512 autoantibodies. |
| 1852 | 12021116 | The results suggest that GAD65 and ICA512 antibody frequencies are neither significantly increased nor decreased in UNDM patients compared to NNDM patients. |
| 1853 | 12021116 | GAD65 and ICA512 antibodies in undernourished and normally nourished south Indian patients with diabetes. |
| 1854 | 12021116 | The frequency of GAD65 and ICA512 antibodies in Indian IDDM patients is similar to that in Caucasians. |
| 1855 | 12021116 | The prevalence of GAD65 and ICA512 autoantibodies in controls from south India was 4% and 2%, respectively. |
| 1856 | 12021116 | One hundred thirty-one diabetic patients (undernourished [UNDM], n = 67; and normal nourished [NNDM], n = 64) were assayed for GAD65 and ICA512 autoantibodies. |
| 1857 | 12021116 | The results suggest that GAD65 and ICA512 antibody frequencies are neither significantly increased nor decreased in UNDM patients compared to NNDM patients. |
| 1858 | 12021116 | GAD65 and ICA512 antibodies in undernourished and normally nourished south Indian patients with diabetes. |
| 1859 | 12021116 | The frequency of GAD65 and ICA512 antibodies in Indian IDDM patients is similar to that in Caucasians. |
| 1860 | 12021116 | The prevalence of GAD65 and ICA512 autoantibodies in controls from south India was 4% and 2%, respectively. |
| 1861 | 12021116 | One hundred thirty-one diabetic patients (undernourished [UNDM], n = 67; and normal nourished [NNDM], n = 64) were assayed for GAD65 and ICA512 autoantibodies. |
| 1862 | 12021116 | The results suggest that GAD65 and ICA512 antibody frequencies are neither significantly increased nor decreased in UNDM patients compared to NNDM patients. |
| 1863 | 12021116 | GAD65 and ICA512 antibodies in undernourished and normally nourished south Indian patients with diabetes. |
| 1864 | 12021116 | The frequency of GAD65 and ICA512 antibodies in Indian IDDM patients is similar to that in Caucasians. |
| 1865 | 12021116 | The prevalence of GAD65 and ICA512 autoantibodies in controls from south India was 4% and 2%, respectively. |
| 1866 | 12021116 | One hundred thirty-one diabetic patients (undernourished [UNDM], n = 67; and normal nourished [NNDM], n = 64) were assayed for GAD65 and ICA512 autoantibodies. |
| 1867 | 12021116 | The results suggest that GAD65 and ICA512 antibody frequencies are neither significantly increased nor decreased in UNDM patients compared to NNDM patients. |
| 1868 | 12021119 | Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. |
| 1869 | 12021119 | One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. |
| 1870 | 12021119 | GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. |
| 1871 | 12021119 | Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). |
| 1872 | 12021119 | Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. |
| 1873 | 12021119 | One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. |
| 1874 | 12021119 | GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. |
| 1875 | 12021119 | Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). |
| 1876 | 12021119 | Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. |
| 1877 | 12021119 | One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. |
| 1878 | 12021119 | GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. |
| 1879 | 12021119 | Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). |
| 1880 | 12021119 | Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. |
| 1881 | 12021119 | One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. |
| 1882 | 12021119 | GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. |
| 1883 | 12021119 | Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). |
| 1884 | 12021124 | Autoantibodies against glutamic acid decarboxylase (GAD65) and tyrosine phosphatase (IA-2) are strongly associated with autoimmune diabetes and can be useful in early identification of the development of type 1 diabetes in women with GDM. |
| 1885 | 12021124 | The aim of our study was to estimate the prevalence of autoantibodies against minor antigens-tissue transglutaminase (TTG), ICA12, and 21-hydroxylase (21-0H)-in GDM patients from southern India. |
| 1886 | 12021124 | Eighty-six serum samples from GDM subjects and 114 samples from healthy controls were tested for the presence of GAD65 and IA-2Ab as well as for the presence of 21-OH, TTG, and ICA12Ab by radiobinding assay with in vitro translated recombinant human 35S-GAD65, IA-2, TTG, ICA12, and 21-OH antigens. |
| 1887 | 12021124 | We observed the presence of GAD65 or IA-2 autoantibodies in 41% (35/86) of GDM patients, while none of the patients tested positive for any of the minor autoantibodies. |
| 1888 | 12021124 | Autoantibodies against glutamic acid decarboxylase (GAD65) and tyrosine phosphatase (IA-2) are strongly associated with autoimmune diabetes and can be useful in early identification of the development of type 1 diabetes in women with GDM. |
| 1889 | 12021124 | The aim of our study was to estimate the prevalence of autoantibodies against minor antigens-tissue transglutaminase (TTG), ICA12, and 21-hydroxylase (21-0H)-in GDM patients from southern India. |
| 1890 | 12021124 | Eighty-six serum samples from GDM subjects and 114 samples from healthy controls were tested for the presence of GAD65 and IA-2Ab as well as for the presence of 21-OH, TTG, and ICA12Ab by radiobinding assay with in vitro translated recombinant human 35S-GAD65, IA-2, TTG, ICA12, and 21-OH antigens. |
| 1891 | 12021124 | We observed the presence of GAD65 or IA-2 autoantibodies in 41% (35/86) of GDM patients, while none of the patients tested positive for any of the minor autoantibodies. |
| 1892 | 12021124 | Autoantibodies against glutamic acid decarboxylase (GAD65) and tyrosine phosphatase (IA-2) are strongly associated with autoimmune diabetes and can be useful in early identification of the development of type 1 diabetes in women with GDM. |
| 1893 | 12021124 | The aim of our study was to estimate the prevalence of autoantibodies against minor antigens-tissue transglutaminase (TTG), ICA12, and 21-hydroxylase (21-0H)-in GDM patients from southern India. |
| 1894 | 12021124 | Eighty-six serum samples from GDM subjects and 114 samples from healthy controls were tested for the presence of GAD65 and IA-2Ab as well as for the presence of 21-OH, TTG, and ICA12Ab by radiobinding assay with in vitro translated recombinant human 35S-GAD65, IA-2, TTG, ICA12, and 21-OH antigens. |
| 1895 | 12021124 | We observed the presence of GAD65 or IA-2 autoantibodies in 41% (35/86) of GDM patients, while none of the patients tested positive for any of the minor autoantibodies. |
| 1896 | 12021125 | Autoantibodies against major antigens GAD65 and IA-2 as well as some minor antibodies are markers for autoimmune diabetes already several years before clinical onset in most populations. |
| 1897 | 12021125 | The aim of our study was to detect the presence of glutamic acid decarboxylase (GAD65), tyrosine phosphates (IA-2) and tissue transglutaminase (TTG) antibodies. |
| 1898 | 12021125 | Autoantibodies against major antigens GAD65 and IA-2 as well as some minor antibodies are markers for autoimmune diabetes already several years before clinical onset in most populations. |
| 1899 | 12021125 | The aim of our study was to detect the presence of glutamic acid decarboxylase (GAD65), tyrosine phosphates (IA-2) and tissue transglutaminase (TTG) antibodies. |
| 1900 | 12021126 | Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. |
| 1901 | 12021126 | Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. |
| 1902 | 12021126 | Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). |
| 1903 | 12021126 | At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. |
| 1904 | 12021126 | Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. |
| 1905 | 12021126 | Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. |
| 1906 | 12021126 | Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). |
| 1907 | 12021126 | At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. |
| 1908 | 12021126 | Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. |
| 1909 | 12021126 | Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. |
| 1910 | 12021126 | Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). |
| 1911 | 12021126 | At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. |
| 1912 | 12021126 | Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. |
| 1913 | 12021126 | Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. |
| 1914 | 12021126 | Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). |
| 1915 | 12021126 | At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. |
| 1916 | 12021127 | BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. |
| 1917 | 12021127 | This paper reports a study to determine whether BCG vaccination is associated with an increase or decrease in GAD65 and I-A2 autoantibodies in cases of IDDM and NIDDM in southern India. |
| 1918 | 12021127 | BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. |
| 1919 | 12021127 | This paper reports a study to determine whether BCG vaccination is associated with an increase or decrease in GAD65 and I-A2 autoantibodies in cases of IDDM and NIDDM in southern India. |
| 1920 | 12021128 | Antibodies to GAD65 and IA-2 are the major immunological markers in autoimmune diabetes. |
| 1921 | 12021128 | We studied 88 IDDM patients and 100 NIDDM patients as well as controls for the prevalence of GAD65, IA-2, and ICA12 antibodies by radioligand binding assay (RIA) using (35)S-labeled islet antigens. |
| 1922 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 1923 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 1924 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 1925 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 1926 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 1927 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 1928 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 1929 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 1930 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 1931 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 1932 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 1933 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 1934 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 1935 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 1936 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 1937 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 1938 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 1939 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 1940 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 1941 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 1942 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 1943 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 1944 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 1945 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 1946 | 12021138 | MHC class I chain-related gene a alleles distinguish malnutrition-modulated diabetes, insulin-dependent diabetes, and non-insulin- dependent diabetes mellitus patients from eastern India. |
| 1947 | 12021138 | Insulin-dependent diabetes mellitus (IDDM) is a polygenic disorder with an autoimmune basis for disease development. |
| 1948 | 12021138 | In addition to HLA, a second susceptibility locus for IDDM has been identified to lie in the major histocompatibility class III region. |
| 1949 | 12021138 | MIC-A is located in the MHC class III region and is expressed by monocytes, keratinocytes, and endothelial cells. |
| 1950 | 12021138 | The aim of our study was to find the association of MIC-A alleles with IDDM, malnutrition-modulated diabetes mellitus (MMDM), and non-insulin-dependent diabetes mellitus (NIDDM) patients. |
| 1951 | 12021138 | Of the 212 NIDDM patients analyzed, 96 of them were found to be positive for either GAD65 or IA-2 antibodies. |
| 1952 | 12021138 | Autoantibodies to GAD65 and IA-2 were measured by radioligand binding assay using (35)S-labeled recombinant human GAD65 and IA-2 in an in vitro transcription/translation system. |
| 1953 | 12021138 | MIC-A alleles distinguish acute-onset IDDM from slow-onset IDDM, indicating that this molecule may be important for delaying the onset of IDDM with the result that these patients are diagnosed clinically as NIDDM. |
| 1954 | 12021138 | MHC class I chain-related gene a alleles distinguish malnutrition-modulated diabetes, insulin-dependent diabetes, and non-insulin- dependent diabetes mellitus patients from eastern India. |
| 1955 | 12021138 | Insulin-dependent diabetes mellitus (IDDM) is a polygenic disorder with an autoimmune basis for disease development. |
| 1956 | 12021138 | In addition to HLA, a second susceptibility locus for IDDM has been identified to lie in the major histocompatibility class III region. |
| 1957 | 12021138 | MIC-A is located in the MHC class III region and is expressed by monocytes, keratinocytes, and endothelial cells. |
| 1958 | 12021138 | The aim of our study was to find the association of MIC-A alleles with IDDM, malnutrition-modulated diabetes mellitus (MMDM), and non-insulin-dependent diabetes mellitus (NIDDM) patients. |
| 1959 | 12021138 | Of the 212 NIDDM patients analyzed, 96 of them were found to be positive for either GAD65 or IA-2 antibodies. |
| 1960 | 12021138 | Autoantibodies to GAD65 and IA-2 were measured by radioligand binding assay using (35)S-labeled recombinant human GAD65 and IA-2 in an in vitro transcription/translation system. |
| 1961 | 12021138 | MIC-A alleles distinguish acute-onset IDDM from slow-onset IDDM, indicating that this molecule may be important for delaying the onset of IDDM with the result that these patients are diagnosed clinically as NIDDM. |
| 1962 | 12021141 | From our previous studies, we have shown that microsatellite allele A5 of MICA is associated with IDDM. |
| 1963 | 12021141 | Out of 100 clinically diagnosed NIDDM patients, 49 tested positive for GAD65 and IA-2 antibodies by use of 35S RIA. |
| 1964 | 12021141 | Our results show that MICA allele A5.1 is significantly increased in antibody-positive (GAD65 or IA-2) NIDDM patients [35/49 (72%)] when compared to healthy controls [22/96 (23%)] (OR = 8.4; P < 0.0001). |
| 1965 | 12021141 | From our previous studies, we have shown that microsatellite allele A5 of MICA is associated with IDDM. |
| 1966 | 12021141 | Out of 100 clinically diagnosed NIDDM patients, 49 tested positive for GAD65 and IA-2 antibodies by use of 35S RIA. |
| 1967 | 12021141 | Our results show that MICA allele A5.1 is significantly increased in antibody-positive (GAD65 or IA-2) NIDDM patients [35/49 (72%)] when compared to healthy controls [22/96 (23%)] (OR = 8.4; P < 0.0001). |
| 1968 | 12073931 | Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65) autoantibodies: a study of Chinese patients with diabetes mellitus. |
| 1969 | 12092457 | Multiple international workshops fostered the development of specific and sensitive radioassays for autoantibodies reacting with GAD65 (glutamic acid decarboxylase), ICA512 (also termed IA-2, a tyrosine phosphatase-like protein), and insulin. |
| 1970 | 12150938 | PDX-1 mediates glucose responsiveness of GAD(67), but not GAD(65), gene transcription in islets of Langerhans. |
| 1971 | 12150938 | Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1. |
| 1972 | 12150938 | We have studied the mRNA level of two isoforms of GAD, GAD(65) and GAD(67), and found that GAD(67) but not GAD(65) mRNA steady-state level is regulated by glucose. |
| 1973 | 12150938 | We show that PDX-1 is able to bind to two TAAT-boxes in the GAD(67) promoter and that functional disruption of these two PDX-1 binding elements has an additive effect in severely impairing glucose responsiveness of the GAD(67) promoter. |
| 1974 | 12150938 | These data strongly suggest that PDX-1 is involved in glucose-regulated expression of GAD(67). |
| 1975 | 12186840 | CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer. |
| 1976 | 12186840 | These mice have GAD65-specific CD4(+) T cells, as shown by staining with an I-A(g7)(p286) tetramer reagent. |
| 1977 | 12186840 | Lymphocytes from these TCR transgenic mice proliferate and make interferon gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-10 when stimulated in vitro with GAD65 peptide 286-300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. |
| 1978 | 12186840 | Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. |
| 1979 | 12186840 | CD4(+) T cells, or p286-tetramer(+)CD4(+) Tcells, from GAD65 286-300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. |
| 1980 | 12186840 | CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer. |
| 1981 | 12186840 | These mice have GAD65-specific CD4(+) T cells, as shown by staining with an I-A(g7)(p286) tetramer reagent. |
| 1982 | 12186840 | Lymphocytes from these TCR transgenic mice proliferate and make interferon gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-10 when stimulated in vitro with GAD65 peptide 286-300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. |
| 1983 | 12186840 | Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. |
| 1984 | 12186840 | CD4(+) T cells, or p286-tetramer(+)CD4(+) Tcells, from GAD65 286-300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. |
| 1985 | 12186840 | CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer. |
| 1986 | 12186840 | These mice have GAD65-specific CD4(+) T cells, as shown by staining with an I-A(g7)(p286) tetramer reagent. |
| 1987 | 12186840 | Lymphocytes from these TCR transgenic mice proliferate and make interferon gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-10 when stimulated in vitro with GAD65 peptide 286-300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. |
| 1988 | 12186840 | Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. |
| 1989 | 12186840 | CD4(+) T cells, or p286-tetramer(+)CD4(+) Tcells, from GAD65 286-300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. |
| 1990 | 12197888 | Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. |
| 1991 | 12197888 | To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. |
| 1992 | 12197888 | These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases. |
| 1993 | 12197888 | Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. |
| 1994 | 12197888 | To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. |
| 1995 | 12197888 | These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases. |
| 1996 | 12355780 | [Autoantibodies against GAD, GAD65 and IA-2]. |
| 1997 | 12369720 | The serum samples were incubated with the specific antigen (GAD65, IA-2 or insulin) and the ICA analysis and the corresponding immunoprecipitation assay were performed before and after the absorption. |
| 1998 | 12369720 | We could then demonstrate that specific autoantibodies against GAD65 and IA-2 could be absorbed with the corresponding antigen, since ten GADA positive and six IA-2A samples turned completely negative. |
| 1999 | 12369720 | The results strongly indicate that the ICA reaction represents simultaneous autoimmunity against several other antigens beside GAD65, IA-2 and insulin. |
| 2000 | 12369720 | The serum samples were incubated with the specific antigen (GAD65, IA-2 or insulin) and the ICA analysis and the corresponding immunoprecipitation assay were performed before and after the absorption. |
| 2001 | 12369720 | We could then demonstrate that specific autoantibodies against GAD65 and IA-2 could be absorbed with the corresponding antigen, since ten GADA positive and six IA-2A samples turned completely negative. |
| 2002 | 12369720 | The results strongly indicate that the ICA reaction represents simultaneous autoimmunity against several other antigens beside GAD65, IA-2 and insulin. |
| 2003 | 12369720 | The serum samples were incubated with the specific antigen (GAD65, IA-2 or insulin) and the ICA analysis and the corresponding immunoprecipitation assay were performed before and after the absorption. |
| 2004 | 12369720 | We could then demonstrate that specific autoantibodies against GAD65 and IA-2 could be absorbed with the corresponding antigen, since ten GADA positive and six IA-2A samples turned completely negative. |
| 2005 | 12369720 | The results strongly indicate that the ICA reaction represents simultaneous autoimmunity against several other antigens beside GAD65, IA-2 and insulin. |
| 2006 | 12482194 | Serum was analysed for the presence of the enzyme glutamic acid decarboxylase, isoform 65, (GAD65) and autoantibodies against glutamic acid decarboxylase, isoform 65 (GAD65A), isoform 67 (GAD67A), insulinoma antigen 2 (IA-2) and insulin (IAA). |
| 2007 | 12498766 | Syngeneic splenocytes were transduced with retroviral particles carrying a cDNA construct encoding the beta cell antigen glutamic acid decarboxylase (GAD65), a secreted form of GAD65 (SGAD55), or secreted alkaline phosphatase (SEAP) as a control antigen. |
| 2008 | 12516400 | [Expression of autoantibodies to ICA512 and GAD in the sera of patients with diabetic ketoacidosis or ketonemia]. |
| 2009 | 12516400 | To explore the expression of the autoantibodies to ICA512 and GAD65 in the sera of diabetic patients who will be diagnosed as Type 1 diabetes, autoantibody assays were carried out in 15 diabetic patients complicated with ketonemia or ketoacidosis and in 19 healthy controls. |
| 2010 | 12524658 | Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed as predictive markers of type 1 diabetes mellitus. |
| 2011 | 12524658 | GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed children and the prevalence was not different in relationship to clinical characteristics. |
| 2012 | 12524658 | Levels of GAD(65) Ab positively correlated with diagnosis age (P <.05). |
| 2013 | 12524658 | Among the cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2 Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed children, respectively) and more patients were identified by these Ab (68%) than by ICA alone (34%) (P <.05). |
| 2014 | 12524658 | In this cohort, levels of ICA512/IA-2 Ab negatively correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with daily insulin requirement (P <.05). |
| 2015 | 12524658 | Our findings confirm that positivity for either GAD(65) or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group, identifying a group of patients with absent ICA immunofluorescence. |
| 2016 | 12524658 | Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed as predictive markers of type 1 diabetes mellitus. |
| 2017 | 12524658 | GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed children and the prevalence was not different in relationship to clinical characteristics. |
| 2018 | 12524658 | Levels of GAD(65) Ab positively correlated with diagnosis age (P <.05). |
| 2019 | 12524658 | Among the cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2 Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed children, respectively) and more patients were identified by these Ab (68%) than by ICA alone (34%) (P <.05). |
| 2020 | 12524658 | In this cohort, levels of ICA512/IA-2 Ab negatively correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with daily insulin requirement (P <.05). |
| 2021 | 12524658 | Our findings confirm that positivity for either GAD(65) or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group, identifying a group of patients with absent ICA immunofluorescence. |
| 2022 | 12524658 | Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed as predictive markers of type 1 diabetes mellitus. |
| 2023 | 12524658 | GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed children and the prevalence was not different in relationship to clinical characteristics. |
| 2024 | 12524658 | Levels of GAD(65) Ab positively correlated with diagnosis age (P <.05). |
| 2025 | 12524658 | Among the cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2 Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed children, respectively) and more patients were identified by these Ab (68%) than by ICA alone (34%) (P <.05). |
| 2026 | 12524658 | In this cohort, levels of ICA512/IA-2 Ab negatively correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with daily insulin requirement (P <.05). |
| 2027 | 12524658 | Our findings confirm that positivity for either GAD(65) or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group, identifying a group of patients with absent ICA immunofluorescence. |
| 2028 | 12524658 | Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed as predictive markers of type 1 diabetes mellitus. |
| 2029 | 12524658 | GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed children and the prevalence was not different in relationship to clinical characteristics. |
| 2030 | 12524658 | Levels of GAD(65) Ab positively correlated with diagnosis age (P <.05). |
| 2031 | 12524658 | Among the cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2 Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed children, respectively) and more patients were identified by these Ab (68%) than by ICA alone (34%) (P <.05). |
| 2032 | 12524658 | In this cohort, levels of ICA512/IA-2 Ab negatively correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with daily insulin requirement (P <.05). |
| 2033 | 12524658 | Our findings confirm that positivity for either GAD(65) or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group, identifying a group of patients with absent ICA immunofluorescence. |
| 2034 | 12604315 | We have recently reported that in patients with anti-glutamic acid decarboxylase (GAD) 65(+)diabetes with residual beta-cell function, most with a 'high-titer' (>10U/ml) required insulin within 5 years, whereas most with a 'low-titer' (1.3-9.9U/ml) did not need insulin for over 15-20 years after the onset. |
| 2035 | 12604315 | Although GAD65-reactive CD4(+)cells in the periphery were detected in both groups, a significant positive correlation between serum IP-10 level and the number of GAD65-reactive CD4(+)cells was observed only in the high-titer group. |
| 2036 | 12604315 | Therefore, it has been speculated that the co-existence of GAD65-reactive IFN-gamma-producing CD4(+)cells and a high serum IP-10 level may be important for rapid disease progression as seen in the high-titer group. |
| 2037 | 12604315 | We have recently reported that in patients with anti-glutamic acid decarboxylase (GAD) 65(+)diabetes with residual beta-cell function, most with a 'high-titer' (>10U/ml) required insulin within 5 years, whereas most with a 'low-titer' (1.3-9.9U/ml) did not need insulin for over 15-20 years after the onset. |
| 2038 | 12604315 | Although GAD65-reactive CD4(+)cells in the periphery were detected in both groups, a significant positive correlation between serum IP-10 level and the number of GAD65-reactive CD4(+)cells was observed only in the high-titer group. |
| 2039 | 12604315 | Therefore, it has been speculated that the co-existence of GAD65-reactive IFN-gamma-producing CD4(+)cells and a high serum IP-10 level may be important for rapid disease progression as seen in the high-titer group. |
| 2040 | 12657523 | Both the CD4(+) and CD8(+) subsets of T cells are required for the normal development of IDDM in NOD mice. |
| 2041 | 12657523 | We have isolated a GAD(65) reactive, cytotoxic CD8(+) T cell clone R1 that produces large quantities of IFNgamma and accelerates the onset of insulitis. |
| 2042 | 12657523 | This clone proliferates and produces IFNgamma in response to GAD(65) presenting APCs and kills GAD(65) presenting targets. |
| 2043 | 12657523 | Furthermore, it expresses TNFalpha, CD25, CD28, CD44, CD45 and LFA1, but not CD95L This is the first example of a GAD(65)specific CD8(+) T cell clone that accelerates the onset of the insulitis, although it does not appear to accelerate the onset of diabetes. |
| 2044 | 12672406 | To address this, antibody titer and subclass to insulin, glutamic acid decarboxylase (GAD)65, IA-2, and IA-2beta proteins were measured by radiobinding assays in untreated or immunized female nonobese diabetic mice. |
| 2045 | 12672406 | Untreated nonobese diabetic mice developed autoantibodies to insulin (IAA), but not GAD or IA-2/IA-2beta, and IAA-positive mice had increased diabetes risk (P < 0.001). |
| 2046 | 12672406 | In immunized mice, IgG1 and lesser IgG2b insulin antibodies were promoted by subcutaneous injection of insulin plus incomplete Freund's adjuvant, insulin plus Montanide ISA 720, and glucagon plus incomplete Freund's adjuvant, but not by incomplete Freund's adjuvant plus GAD65, IA-2beta, or phenylethanolamine N-methyltransferase, or adjuvant alone. |
| 2047 | 12672406 | Spreading of antibody responses to GAD or IA-2/IA-2beta following immunization was rare, and antibody epitope spreading was only detected in IA-2beta immunized mice. |
| 2048 | 12745667 | Wild bank voles (Clethrionomys glareolus) kept in the laboratory under barren housing conditions develop high incidences of type 1 diabetes mellitus due to beta cell-specific lysis in association with the appearance of GAD65, IA-2, and insulin autoantibodies. |
| 2049 | 12745669 | Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. |
| 2050 | 12745669 | Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P < .0001), IA-2 (P < .0001), and insulin (P = .03) autoantibodies. |
| 2051 | 12745669 | Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. |
| 2052 | 12745669 | Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P < .0001), IA-2 (P < .0001), and insulin (P = .03) autoantibodies. |
| 2053 | 12753809 | A positive correlation between serum hsp90AA and glutamic acid decarboxylase (GAD65) autoantibody (GAA) was also observed. |
| 2054 | 12797903 | Furthermore, the monoclonal antibody against E. coli GAD does not recognise human recombinant GAD65 in an ELISA. |
| 2055 | 12817032 | NOD recipient mice immunized with pDNA encoding a glutamic acid decarboxylase 65 (GAD65)-IgFc fusion protein (JwGAD65), IL-4 (JwIL4), and IL-10 (pIL10) exhibited an increased number of intact pro-islets expressing high levels of insulin 15 wk posttransplant, relative to NOD recipient mice immunized with pDNA encoding a hen egg lysozyme (HEL)-IgFc fusion protein (JwHEL)+JwIL4 and pIL10 or left untreated. |
| 2056 | 12817032 | Efficient protection of pro-islet grafts correlated with a marked reduction in GAD65-specific IFN-gamma reactivity and an increase in IL-10-secreting T cells. |
| 2057 | 12817032 | NOD recipient mice immunized with pDNA encoding a glutamic acid decarboxylase 65 (GAD65)-IgFc fusion protein (JwGAD65), IL-4 (JwIL4), and IL-10 (pIL10) exhibited an increased number of intact pro-islets expressing high levels of insulin 15 wk posttransplant, relative to NOD recipient mice immunized with pDNA encoding a hen egg lysozyme (HEL)-IgFc fusion protein (JwHEL)+JwIL4 and pIL10 or left untreated. |
| 2058 | 12817032 | Efficient protection of pro-islet grafts correlated with a marked reduction in GAD65-specific IFN-gamma reactivity and an increase in IL-10-secreting T cells. |
| 2059 | 14557453 | Disease-specific epitope profiles of glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) were studied in slowly progressive type 1 (insulin-dependent) diabetes mellitus (SPIDDM) and acute onset type 1 (insulin-dependent) diabetes mellitus (AIDDM) using seven kinds of GAD65/67 chimeric molecules. |
| 2060 | 14624759 | Samples from two subjects were pre-tested for responses to sub-optimal concentrations of tetanus toxoid, representing a low frequency recall response, and peptides from diabetes associated autoantigens GAD65, IA-2 and HSP60. |
| 2061 | 14679041 | Both TCR transgenics respond to their cognate peptide/MHC (GAD65 206-220 and 286-300) and produce IL-2, IFN-gamma, and small amounts of IL-10. |
| 2062 | 14679041 | Thus, GAD65 specific TCR transgenic T cells (1) must express a second a chain to survive negative selection, (2) produce IL-2 and IFN-gamma, and (3) have a mildly protective effect on transfer of diabetes with diabetogenic spleen cells. |
| 2063 | 14679041 | Both TCR transgenics respond to their cognate peptide/MHC (GAD65 206-220 and 286-300) and produce IL-2, IFN-gamma, and small amounts of IL-10. |
| 2064 | 14679041 | Thus, GAD65 specific TCR transgenic T cells (1) must express a second a chain to survive negative selection, (2) produce IL-2 and IFN-gamma, and (3) have a mildly protective effect on transfer of diabetes with diabetogenic spleen cells. |
| 2065 | 14679074 | Autoantibodies against GAD(65) (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by radioligand-binding assays. |
| 2066 | 14679074 | Our results suggest that the mechanisms of beta cell tolerance to GAD and IA-2 differ in healthy children. |
| 2067 | 14679080 | In addition, 87 NHW first-degree relatives of type 1 diabetes patients were studied: 33 positive and 54 negative for autoantibodies to insulin, GAD65, or IA-2. |
| 2068 | 14679095 | LADA was identified by a clinical phenotype of type 2 diabetes with antibodies to GAD65 and/or IA-2/ICA512. |
| 2069 | 14679097 | Autoantibodies to GAD65 and IA-2 antibodies are increased, but not tissue transglutaminase (TTG-Ab) in type 2 diabetes mellitus (T2DM) patients from South India. |
| 2070 | 14679097 | In this study, we measured autoantibodies to GAD65, IA-2, and TTG in T2DM patients from Southern India. |
| 2071 | 14679097 | Our results show that either GAD65 or IA-2 was present in 30% of T2DM patients (n = 155) and in 3% of controls for GAD65 and 1% of controls for IA-2 (n = 105). |
| 2072 | 14679097 | Autoantibodies to GAD65 and IA-2 antibodies are increased, but not tissue transglutaminase (TTG-Ab) in type 2 diabetes mellitus (T2DM) patients from South India. |
| 2073 | 14679097 | In this study, we measured autoantibodies to GAD65, IA-2, and TTG in T2DM patients from Southern India. |
| 2074 | 14679097 | Our results show that either GAD65 or IA-2 was present in 30% of T2DM patients (n = 155) and in 3% of controls for GAD65 and 1% of controls for IA-2 (n = 105). |
| 2075 | 14679097 | Autoantibodies to GAD65 and IA-2 antibodies are increased, but not tissue transglutaminase (TTG-Ab) in type 2 diabetes mellitus (T2DM) patients from South India. |
| 2076 | 14679097 | In this study, we measured autoantibodies to GAD65, IA-2, and TTG in T2DM patients from Southern India. |
| 2077 | 14679097 | Our results show that either GAD65 or IA-2 was present in 30% of T2DM patients (n = 155) and in 3% of controls for GAD65 and 1% of controls for IA-2 (n = 105). |
| 2078 | 14679098 | GAD65 and IA-2 autoantibodies were measured by radioligand binding assay using recombinant human GAD65 and IA-2. |
| 2079 | 14725793 | Glutamic acid decarboxylase (GAD65) is one of the autoantigens that initiates pathogenic T cell responses against insulin-secreting pancreatic beta cells in Type 1 diabetes (T1D). |
| 2080 | 15016223 | To determine the prevalence of diabetes autoimmune markers, ICA512, GAD65 and insulin autoantibodies (IAA) antibodies were measured. |
| 2081 | 15016223 | GAD and ICA512 antibody results suggest a relative lack of diabetes immune markers in infants and toddlers with new-onset diabetes. |
| 2082 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 2083 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 2084 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 2085 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 2086 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 2087 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 2088 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 2089 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 2090 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 2091 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 2092 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 2093 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 2094 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 2095 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 2096 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 2097 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 2098 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 2099 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 2100 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 2101 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 2102 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 2103 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 2104 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 2105 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 2106 | 15070923 | The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. |
| 2107 | 15070923 | We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. |
| 2108 | 15070923 | Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. |
| 2109 | 15070923 | The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. |
| 2110 | 15070923 | The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. |
| 2111 | 15070923 | We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. |
| 2112 | 15070923 | Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. |
| 2113 | 15070923 | The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. |
| 2114 | 15070923 | The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. |
| 2115 | 15070923 | We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. |
| 2116 | 15070923 | Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. |
| 2117 | 15070923 | The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. |
| 2118 | 15098924 | Glutamic acid decarboxylase (GAD65 and GAD67) in pancreatic beta cells is the target of autoantibodies and autoreactive T cells in insulin-dependent diabetes mellitus (IDDM). |
| 2119 | 15098924 | Regulating expression of GAD perhaps is a practical approach to treat IDDM. |
| 2120 | 15098924 | In this study, we established an in vitro system, in which GAD was expressed and glutamate treatment produced over-expression of GAD67 and GAD65 in rat islet cells. |
| 2121 | 15098924 | These findings suggest that the over-expression of GAD67 induced by glutamate in islet cells of rat may act as a suitable cellular model to study GAD autoreactivity during the development of IDDM. |
| 2122 | 15098924 | Meanwhile, it indicates that ALC, an ester of the trimethylated amino acid, can block glutamate-induced over-expression of GAD67, a key beta-cell autoantigen, suggesting a therapeutic potential of ALC in IDDM. |
| 2123 | 15098924 | Glutamic acid decarboxylase (GAD65 and GAD67) in pancreatic beta cells is the target of autoantibodies and autoreactive T cells in insulin-dependent diabetes mellitus (IDDM). |
| 2124 | 15098924 | Regulating expression of GAD perhaps is a practical approach to treat IDDM. |
| 2125 | 15098924 | In this study, we established an in vitro system, in which GAD was expressed and glutamate treatment produced over-expression of GAD67 and GAD65 in rat islet cells. |
| 2126 | 15098924 | These findings suggest that the over-expression of GAD67 induced by glutamate in islet cells of rat may act as a suitable cellular model to study GAD autoreactivity during the development of IDDM. |
| 2127 | 15098924 | Meanwhile, it indicates that ALC, an ester of the trimethylated amino acid, can block glutamate-induced over-expression of GAD67, a key beta-cell autoantigen, suggesting a therapeutic potential of ALC in IDDM. |
| 2128 | 15163889 | T cells recognize multiple GAD65 and proinsulin epitopes in human type 1 diabetes, suggesting determinant spreading. |
| 2129 | 15163889 | Using comprehensive peptide libraries that cover the entire sequence of two major candidate autoantigens, GAD65 and proinsulin, we measured the in vivo frequencies of peptide-specific, IFN-gamma-producing memory T cells in 27 diabetic patients, 14 high risk individuals, and 15 partially HLA-matched healthy controls. |
| 2130 | 15163889 | T cells recognize multiple GAD65 and proinsulin epitopes in human type 1 diabetes, suggesting determinant spreading. |
| 2131 | 15163889 | Using comprehensive peptide libraries that cover the entire sequence of two major candidate autoantigens, GAD65 and proinsulin, we measured the in vivo frequencies of peptide-specific, IFN-gamma-producing memory T cells in 27 diabetic patients, 14 high risk individuals, and 15 partially HLA-matched healthy controls. |
| 2132 | 15270809 | Autoantibodies against GAD65 and IA-2 in recently diagnosed Type 1 diabetic children from Western India. |
| 2133 | 15277377 | GAD65-specific CD4+ T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes. |
| 2134 | 15381770 | However, we previously reported that nonobese diabetic (NOD) mice transgenic for a T cell antigen receptor (TCR) specific for one of the immunodominant epitopes of GAD65, peptide 286-300 (G286), are protected from insulitis and diabetes. |
| 2135 | 15381770 | Both G206 and G286 T cells produce immunoregulatory cytokines IFN-gamma and IL-10 at low levels when activated by cognate antigens. |
| 2136 | 15501398 | Expression of cytoplasmic islet cell (ICA), GAD65, ICA512 and insulin autoantibodies in 357 different-sex (DZ) potential non-diabetic twins of T1DM patients was, respectively, 4.5%, 4.7%, 3.0% and 2.4%, which was lower than in 539 same-sex potential non-diabetic twins (including MZ and DZ) of T1DM patients for ICA (7.8%, p < 0.05), GAD65 (13.4%, p < 0.0001) and ICA512 (6.5%, p < 0.03). |
| 2137 | 15501398 | In contrast, expression of ICA, GAD65, ICA512 and insulin autoantibodies was not significantly different in different-sex (DZ) potential twins versus all siblings (respectively, 4.2%, 4.8%, 2.2%, 2.5%), different-sex siblings (3.9%, 4.9%, 2.2%, 2.5%) or same-sex siblings (4.4%, 4.7%, 2.2%, 2.5%) of T1DM patients. |
| 2138 | 15501398 | Expression of cytoplasmic islet cell (ICA), GAD65, ICA512 and insulin autoantibodies in 357 different-sex (DZ) potential non-diabetic twins of T1DM patients was, respectively, 4.5%, 4.7%, 3.0% and 2.4%, which was lower than in 539 same-sex potential non-diabetic twins (including MZ and DZ) of T1DM patients for ICA (7.8%, p < 0.05), GAD65 (13.4%, p < 0.0001) and ICA512 (6.5%, p < 0.03). |
| 2139 | 15501398 | In contrast, expression of ICA, GAD65, ICA512 and insulin autoantibodies was not significantly different in different-sex (DZ) potential twins versus all siblings (respectively, 4.2%, 4.8%, 2.2%, 2.5%), different-sex siblings (3.9%, 4.9%, 2.2%, 2.5%) or same-sex siblings (4.4%, 4.7%, 2.2%, 2.5%) of T1DM patients. |
| 2140 | 15531528 | GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 nondiabetic patient controls. |
| 2141 | 15531528 | Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. |
| 2142 | 15531528 | GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 nondiabetic patient controls. |
| 2143 | 15531528 | Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. |
| 2144 | 15549775 | Inhibition of altered peptide ligand-mediated antagonism of human GAD65-responsive CD4+ T cells by non-antagonizable T cells. |
| 2145 | 15549775 | In this study we identified several altered peptide ligands derived from the type 1 diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65) epitope that were capable of antagonizing a subset of a panel of human CD4(+) GAD65 (555-567)-responsive T cell clones derived from a diabetic individual. |
| 2146 | 15549775 | Inhibition of altered peptide ligand-mediated antagonism of human GAD65-responsive CD4+ T cells by non-antagonizable T cells. |
| 2147 | 15549775 | In this study we identified several altered peptide ligands derived from the type 1 diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65) epitope that were capable of antagonizing a subset of a panel of human CD4(+) GAD65 (555-567)-responsive T cell clones derived from a diabetic individual. |
| 2148 | 15564450 | This epitope is recognized by effector memory (gamma interferon [IFN-gamma]-producing) CD8 T cells in the peripheral blood at a frequency of responders that suggests that it is a major focus of the anti-CVB4 response. |
| 2149 | 15564450 | However, P2C(1137-1145)-specific cytotoxic T lymphocyte (CTL) lines were not activated to produce IFN-gamma by the GAD(65) peptide homologue and did not show cytotoxic activity in the presence of appropriately labeled targets. |
| 2150 | 15629156 | The antigenic epitopes within GAD65(448-585), GAD65(487-585), and GAD65(512-585) against insulin-dependent diabetes mellitus (IDDM) marker (autoantibodies against GAD65) were localized at the surface of the spherical protein nanoparticles so that anti-GAD65 Ab could recognize them. |
| 2151 | 15671113 | The fetal insulin hypothesis proposes that low birth weight might be mediated partly by genetic factors that impair insulin secretion/sensitivity during the fetal stage, as shown for glucokinase, the ATP-sensitive K+ channel subunit Kir6.2, and the small heterodimer partner genes. |
| 2152 | 15671113 | Glutamic acid decarboxylase 2 gene (GAD2) overexpression impairs insulin secretion in animals. |
| 2153 | 15671113 | In the present study, we investigated potential effects of the functional -243 A-->G polymorphism in the 5' promoter region of the GAD2 gene on fetal growth, insulin secretion, food intake, and risk of obesity in 635 French Caucasian severely obese children from three different medical centers. |
| 2154 | 15671113 | These results confirm the association between GAD2-243 promoter SNP and the risk for obesity and suggest that GAD2 may be a polygenic component of the complex mechanisms linking birth weight to further risk for metabolic diseases, possibly involving the pleiotropic effect of insulin on fetal growth and later on feeding behavior. |
| 2155 | 15671113 | The fetal insulin hypothesis proposes that low birth weight might be mediated partly by genetic factors that impair insulin secretion/sensitivity during the fetal stage, as shown for glucokinase, the ATP-sensitive K+ channel subunit Kir6.2, and the small heterodimer partner genes. |
| 2156 | 15671113 | Glutamic acid decarboxylase 2 gene (GAD2) overexpression impairs insulin secretion in animals. |
| 2157 | 15671113 | In the present study, we investigated potential effects of the functional -243 A-->G polymorphism in the 5' promoter region of the GAD2 gene on fetal growth, insulin secretion, food intake, and risk of obesity in 635 French Caucasian severely obese children from three different medical centers. |
| 2158 | 15671113 | These results confirm the association between GAD2-243 promoter SNP and the risk for obesity and suggest that GAD2 may be a polygenic component of the complex mechanisms linking birth weight to further risk for metabolic diseases, possibly involving the pleiotropic effect of insulin on fetal growth and later on feeding behavior. |
| 2159 | 15671113 | The fetal insulin hypothesis proposes that low birth weight might be mediated partly by genetic factors that impair insulin secretion/sensitivity during the fetal stage, as shown for glucokinase, the ATP-sensitive K+ channel subunit Kir6.2, and the small heterodimer partner genes. |
| 2160 | 15671113 | Glutamic acid decarboxylase 2 gene (GAD2) overexpression impairs insulin secretion in animals. |
| 2161 | 15671113 | In the present study, we investigated potential effects of the functional -243 A-->G polymorphism in the 5' promoter region of the GAD2 gene on fetal growth, insulin secretion, food intake, and risk of obesity in 635 French Caucasian severely obese children from three different medical centers. |
| 2162 | 15671113 | These results confirm the association between GAD2-243 promoter SNP and the risk for obesity and suggest that GAD2 may be a polygenic component of the complex mechanisms linking birth weight to further risk for metabolic diseases, possibly involving the pleiotropic effect of insulin on fetal growth and later on feeding behavior. |
| 2163 | 15683454 | Using the sensitive enzyme-linked immunospot (ELISPOT) technique to divide Th1- from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 was analysed from lymphocytes spontaneously and after in vitro stimulation with different antigens, based on present paradigms regarding the pathogenesis of type 1 diabetes. |
| 2164 | 15683454 | Compared to the response observed in healthy individuals, we found that individuals with a high risk of developing type 1 diabetes, especially children, responded with less IFN-gamma secretion to the three autoantigens glutamic acid decarboxylase 65 (GAD65), insulin and tyrosinphosphatase (IA-2). |
| 2165 | 15690345 | The 65 kDa human isoform of glutamate decarboxylase, GAD65, plays a central role in neurotransmission in higher vertebrates and is a typical autoantigen in several human autoimmune diseases, such as insulin-dependent diabetes mellitus (IDDM), Stiff-man syndrome and autoimmune polyendocrine syndrome type I. |
| 2166 | 15690345 | Herein a model of GAD65 is presented, which is based on the recently solved crystal structures of mammalian DOPA decarboxylase and of bacterial glutamate decarboxylase. |
| 2167 | 15690345 | The 65 kDa human isoform of glutamate decarboxylase, GAD65, plays a central role in neurotransmission in higher vertebrates and is a typical autoantigen in several human autoimmune diseases, such as insulin-dependent diabetes mellitus (IDDM), Stiff-man syndrome and autoimmune polyendocrine syndrome type I. |
| 2168 | 15690345 | Herein a model of GAD65 is presented, which is based on the recently solved crystal structures of mammalian DOPA decarboxylase and of bacterial glutamate decarboxylase. |
| 2169 | 15699488 | CD4+ T cell proliferation in response to GAD and proinsulin in healthy, pre-diabetic, and diabetic donors. |
| 2170 | 15699488 | However, peripheral blood cells from healthy, pre-diabetic and diabetic donors exhibited overlap in responses to glutamic acid decarboxylase (GAD65) and proinsulin (PI). |
| 2171 | 15717840 | Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. |
| 2172 | 15728483 | Different diabetogenic potential of autoaggressive CD8+ clones associated with IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not cytokine expression, cytolytic activity, or homing characteristics. |
| 2173 | 15728483 | From studies in animal models, CD8(+) T cells recognizing autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit-related protein, insulin, or glutamic acid decarboxylase (GAD) are believed to play important roles in both the early and late phases of beta cell destruction. |
| 2174 | 15728483 | In this study, we investigated the factors governing the diabetogenic potential of autoreactive CD8(+) clones isolated from spleens of NOD mice that had been immunized with GAD65(515-524) or insulin B-chain(15-23) peptides. |
| 2175 | 15728483 | Although these two clones were identical in most phenotypic and functional aspects, for example cytokine production and killing of autologous beta cells, they differed in the expression of IFN-gamma-inducible protein-10, which was only produced at high levels by the insulin-specific clone, but not by the GAD65-specific clone, and other autoantigen-specific nonpathogenic CD8 T cell clones. |
| 2176 | 15728483 | Interestingly, upon i.p. injection into neonatal mice, only the insulin B-chain(15-23)-reactive CD8(+) T clone accelerated diabetes in all recipients after 4 wk, although both insulin- and GAD-reactive clones homed to pancreas and pancreatic lymph nodes with similar kinetics. |
| 2177 | 15728483 | Thus, secretion of IFN-gamma-inducible protein-10 by autoaggressive CD8(+) lymphocytes might determine their diabetogenic capacity by affecting recruitment of cells to the insulitic lesion. |
| 2178 | 15728483 | Different diabetogenic potential of autoaggressive CD8+ clones associated with IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not cytokine expression, cytolytic activity, or homing characteristics. |
| 2179 | 15728483 | From studies in animal models, CD8(+) T cells recognizing autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit-related protein, insulin, or glutamic acid decarboxylase (GAD) are believed to play important roles in both the early and late phases of beta cell destruction. |
| 2180 | 15728483 | In this study, we investigated the factors governing the diabetogenic potential of autoreactive CD8(+) clones isolated from spleens of NOD mice that had been immunized with GAD65(515-524) or insulin B-chain(15-23) peptides. |
| 2181 | 15728483 | Although these two clones were identical in most phenotypic and functional aspects, for example cytokine production and killing of autologous beta cells, they differed in the expression of IFN-gamma-inducible protein-10, which was only produced at high levels by the insulin-specific clone, but not by the GAD65-specific clone, and other autoantigen-specific nonpathogenic CD8 T cell clones. |
| 2182 | 15728483 | Interestingly, upon i.p. injection into neonatal mice, only the insulin B-chain(15-23)-reactive CD8(+) T clone accelerated diabetes in all recipients after 4 wk, although both insulin- and GAD-reactive clones homed to pancreas and pancreatic lymph nodes with similar kinetics. |
| 2183 | 15728483 | Thus, secretion of IFN-gamma-inducible protein-10 by autoaggressive CD8(+) lymphocytes might determine their diabetogenic capacity by affecting recruitment of cells to the insulitic lesion. |
| 2184 | 15814672 | Tolerance induction of autoreactive T cells against pancreatic beta cell-specific autoantigens such as glutamic acid decarboxylase 65 (GAD65) and insulin has been attempted as a method to prevent autoimmune diabetes. |
| 2185 | 15814672 | In this study, we investigate whether adenoassociated virus (AAV) gene delivery of multiple immunodominant epitopes expressing GAD(500-585) could induce potent immune tolerance and persistently suppress autoimmune diabetes in NOD mice. |
| 2186 | 15814672 | This prevention was marked by the inactivation of GAD(500-585)-responsive T lymphocytes, the enhanced GAD(500-585)-specific Th2 response (characterized by increased IL-4, IL-10 production, and decreased IFN-gamma production; especially elevated anti-GAD(500-585) IgG1 titer; and relatively unchanged anti-GAD(500-585) IgG2b titer), the increased secretion of TGF-beta, and the production of protective regulatory cells. |
| 2187 | 15814672 | These data indicate that using AAV, a vector with advantage for therapeutic gene delivery, to transfer autoantigen peptide GAD(500-585), can induce immunological tolerance through active suppression of effector T cells and prevent type I diabetes in NOD mice. |
| 2188 | 15829408 | Absence of avidity maturation of autoantibodies to the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes. |
| 2189 | 15829408 | To assess whether the analysis of the avidity of autoantibodies against the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) could improve the accuracy of risk assessment of progression to clinical type 1 diabetes, we established methods for the determination of the autoantibody avidity based on our previously developed time-resolved fluorometric IA-2 and GAD65 autoantibody (IA-2A and GADA) assays. |
| 2190 | 15829408 | Absence of avidity maturation of autoantibodies to the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes. |
| 2191 | 15829408 | To assess whether the analysis of the avidity of autoantibodies against the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) could improve the accuracy of risk assessment of progression to clinical type 1 diabetes, we established methods for the determination of the autoantibody avidity based on our previously developed time-resolved fluorometric IA-2 and GAD65 autoantibody (IA-2A and GADA) assays. |
| 2192 | 15963796 | Sensitive non-isotopic assays for autoantibodies to IA-2 and to a combination of both IA-2 and GAD65. |
| 2193 | 16009268 | All sera from Group A reacted with GAD(65) protein on Western blots. |
| 2194 | 16009268 | Furthermore, our results suggest that HLA-DRB1*1502-DQB1*0601 or DRB1*1501-DQB1*0602/DRB1*0405-DQB1*0401 heterozygous genotypes may be associated with high production of anti-GADab that recognizes the linear epitope(s) on the GAD(65) protein. |
| 2195 | 16009268 | All sera from Group A reacted with GAD(65) protein on Western blots. |
| 2196 | 16009268 | Furthermore, our results suggest that HLA-DRB1*1502-DQB1*0601 or DRB1*1501-DQB1*0602/DRB1*0405-DQB1*0401 heterozygous genotypes may be associated with high production of anti-GADab that recognizes the linear epitope(s) on the GAD(65) protein. |
| 2197 | 16148057 | Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). |
| 2198 | 16148057 | Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. |
| 2199 | 16148057 | The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. |
| 2200 | 16148057 | Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). |
| 2201 | 16148057 | Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. |
| 2202 | 16148057 | The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. |
| 2203 | 16153889 | Autoantibodies against GAD65 (Mr 65.000 isoform of glutamic acid decarboxylase), IA-2 (insulinoma-associated protein IA-2) or insulin, alone or in combination, predict disease. |
| 2204 | 16177033 | Insulin inhibits neuropeptide Y gene expression in the arcuate nucleus through GABAergic systems. |
| 2205 | 16177033 | Conversely, insulin (10(-11) to 10(-9) M) significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was abolished in the presence of TTX. |
| 2206 | 16177033 | The GABAB agonist baclofen significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was completely abolished in the presence of either the GABAA antagonist bicuculline or the GABAB antagonist CGP35348 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid). |
| 2207 | 16177033 | Furthermore, increases in the GABA-synthesizing enzyme glutamic acid decarboxylase 65 (GAD65) mRNA expression preceded decreases in NPY mRNA expression in the arcuate nucleus in the cultures. |
| 2208 | 16177033 | Experiments in vivo also demonstrated that increases in GAD65 mRNA expression in the arcuate nucleus preceded decreases in the NPY mRNA expression in a fasting-refeeding paradigm and that intracerebroventricular injection of insulin increased GAD65 mRNA expression in the arcuate nucleus in fasted rats. |
| 2209 | 16177033 | These data suggest that insulin inhibits NPY gene expression in the arcuate nucleus through GABAergic systems. |
| 2210 | 16177033 | Insulin inhibits neuropeptide Y gene expression in the arcuate nucleus through GABAergic systems. |
| 2211 | 16177033 | Conversely, insulin (10(-11) to 10(-9) M) significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was abolished in the presence of TTX. |
| 2212 | 16177033 | The GABAB agonist baclofen significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was completely abolished in the presence of either the GABAA antagonist bicuculline or the GABAB antagonist CGP35348 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid). |
| 2213 | 16177033 | Furthermore, increases in the GABA-synthesizing enzyme glutamic acid decarboxylase 65 (GAD65) mRNA expression preceded decreases in NPY mRNA expression in the arcuate nucleus in the cultures. |
| 2214 | 16177033 | Experiments in vivo also demonstrated that increases in GAD65 mRNA expression in the arcuate nucleus preceded decreases in the NPY mRNA expression in a fasting-refeeding paradigm and that intracerebroventricular injection of insulin increased GAD65 mRNA expression in the arcuate nucleus in fasted rats. |
| 2215 | 16177033 | These data suggest that insulin inhibits NPY gene expression in the arcuate nucleus through GABAergic systems. |
| 2216 | 16206515 | We examined the heritability of autoantibodies to glutamic acid decarboxylase (GAD65) in type 1 diabetes, and to thyroglobulin (Tg) in chronic lymphocytic thyroiditis and thyrotoxicosis, using regression of offspring on midparent (ROMP) methods. |
| 2217 | 16236123 | Particular interest has focused on the CVB4 non-structural protein P2C, which we previously showed to be a major target of the effector memory anti-CVB4 CD4 T-cell response, and which harbours a region of sequence similarity with the islet autoantigen, glutamic acid decarboxylase (GAD65). |
| 2218 | 16236123 | In the present study therefore we examined the affinity of 20-mer overlapping P2C peptides for soluble HLA-DR4, -DR3, -DQ2 and -DQ8. |
| 2219 | 16236123 | DR4 and DQ8, P =0.0076; DR3 and DQ2 P = 0.002). |
| 2220 | 16249070 | Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. |
| 2221 | 16249070 | The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. |
| 2222 | 16249070 | A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects. |
| 2223 | 16249070 | In contrast, three quarters of subjects in both groups had tetramer-positive T cells resulting from stimulation of the CD4+CD25+ regulatory T-cell depleted CD4+ T cells. |
| 2224 | 16249070 | These findings suggested that there is no difference in thymic selection of DR4 restricted GAD-reactive T cells amongst healthy and T1D individuals but GAD65(555-567)-reactive T cells have been preferentially activated in diabetic patients. |
| 2225 | 16249070 | Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. |
| 2226 | 16249070 | The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. |
| 2227 | 16249070 | A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects. |
| 2228 | 16249070 | In contrast, three quarters of subjects in both groups had tetramer-positive T cells resulting from stimulation of the CD4+CD25+ regulatory T-cell depleted CD4+ T cells. |
| 2229 | 16249070 | These findings suggested that there is no difference in thymic selection of DR4 restricted GAD-reactive T cells amongst healthy and T1D individuals but GAD65(555-567)-reactive T cells have been preferentially activated in diabetic patients. |
| 2230 | 16249070 | Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. |
| 2231 | 16249070 | The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. |
| 2232 | 16249070 | A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects. |
| 2233 | 16249070 | In contrast, three quarters of subjects in both groups had tetramer-positive T cells resulting from stimulation of the CD4+CD25+ regulatory T-cell depleted CD4+ T cells. |
| 2234 | 16249070 | These findings suggested that there is no difference in thymic selection of DR4 restricted GAD-reactive T cells amongst healthy and T1D individuals but GAD65(555-567)-reactive T cells have been preferentially activated in diabetic patients. |
| 2235 | 16249070 | Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. |
| 2236 | 16249070 | The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. |
| 2237 | 16249070 | A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects. |
| 2238 | 16249070 | In contrast, three quarters of subjects in both groups had tetramer-positive T cells resulting from stimulation of the CD4+CD25+ regulatory T-cell depleted CD4+ T cells. |
| 2239 | 16249070 | These findings suggested that there is no difference in thymic selection of DR4 restricted GAD-reactive T cells amongst healthy and T1D individuals but GAD65(555-567)-reactive T cells have been preferentially activated in diabetic patients. |
| 2240 | 16263242 | GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. |
| 2241 | 16263242 | In this study we have analyzed the prevalence of glutamate decarboxylase 65 (GAD65)- and proinsulin-specific CD4(+) T-cells in type 1 diabetes patients, at-risk subjects and in HLA-matched control children. |
| 2242 | 16263242 | Peripheral blood mononuclear cells were cultured in the presence of two different GAD65 peptides (555-567, 557I and 274-286) or with a proinsulin (B24-C36) peptide for 10-11days. |
| 2243 | 16263242 | Our results show that 11 of 18 (61%) type 1 diabetes patients and 7 of the 20 (35%) at-risk subjects were positive for one of the three GAD65 or proinsulin-containing tetramers, whereas only 2 of 21 (9.5%) controls had tetramer binding cells (p = 0.0007 type 1 diabetes vs. controls and p = 0.0488 at-risk subjects vs. controls, Chi-square test). |
| 2244 | 16263242 | In conclusion, type 1 diabetes patients and at-risk subjects have a significantly higher prevalence of GAD65- and proinsulin-specific CD4(+) T-cells than the control subjects. |
| 2245 | 16263242 | GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. |
| 2246 | 16263242 | In this study we have analyzed the prevalence of glutamate decarboxylase 65 (GAD65)- and proinsulin-specific CD4(+) T-cells in type 1 diabetes patients, at-risk subjects and in HLA-matched control children. |
| 2247 | 16263242 | Peripheral blood mononuclear cells were cultured in the presence of two different GAD65 peptides (555-567, 557I and 274-286) or with a proinsulin (B24-C36) peptide for 10-11days. |
| 2248 | 16263242 | Our results show that 11 of 18 (61%) type 1 diabetes patients and 7 of the 20 (35%) at-risk subjects were positive for one of the three GAD65 or proinsulin-containing tetramers, whereas only 2 of 21 (9.5%) controls had tetramer binding cells (p = 0.0007 type 1 diabetes vs. controls and p = 0.0488 at-risk subjects vs. controls, Chi-square test). |
| 2249 | 16263242 | In conclusion, type 1 diabetes patients and at-risk subjects have a significantly higher prevalence of GAD65- and proinsulin-specific CD4(+) T-cells than the control subjects. |
| 2250 | 16263242 | GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. |
| 2251 | 16263242 | In this study we have analyzed the prevalence of glutamate decarboxylase 65 (GAD65)- and proinsulin-specific CD4(+) T-cells in type 1 diabetes patients, at-risk subjects and in HLA-matched control children. |
| 2252 | 16263242 | Peripheral blood mononuclear cells were cultured in the presence of two different GAD65 peptides (555-567, 557I and 274-286) or with a proinsulin (B24-C36) peptide for 10-11days. |
| 2253 | 16263242 | Our results show that 11 of 18 (61%) type 1 diabetes patients and 7 of the 20 (35%) at-risk subjects were positive for one of the three GAD65 or proinsulin-containing tetramers, whereas only 2 of 21 (9.5%) controls had tetramer binding cells (p = 0.0007 type 1 diabetes vs. controls and p = 0.0488 at-risk subjects vs. controls, Chi-square test). |
| 2254 | 16263242 | In conclusion, type 1 diabetes patients and at-risk subjects have a significantly higher prevalence of GAD65- and proinsulin-specific CD4(+) T-cells than the control subjects. |
| 2255 | 16263242 | GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. |
| 2256 | 16263242 | In this study we have analyzed the prevalence of glutamate decarboxylase 65 (GAD65)- and proinsulin-specific CD4(+) T-cells in type 1 diabetes patients, at-risk subjects and in HLA-matched control children. |
| 2257 | 16263242 | Peripheral blood mononuclear cells were cultured in the presence of two different GAD65 peptides (555-567, 557I and 274-286) or with a proinsulin (B24-C36) peptide for 10-11days. |
| 2258 | 16263242 | Our results show that 11 of 18 (61%) type 1 diabetes patients and 7 of the 20 (35%) at-risk subjects were positive for one of the three GAD65 or proinsulin-containing tetramers, whereas only 2 of 21 (9.5%) controls had tetramer binding cells (p = 0.0007 type 1 diabetes vs. controls and p = 0.0488 at-risk subjects vs. controls, Chi-square test). |
| 2259 | 16263242 | In conclusion, type 1 diabetes patients and at-risk subjects have a significantly higher prevalence of GAD65- and proinsulin-specific CD4(+) T-cells than the control subjects. |
| 2260 | 16280641 | Insulin, glutamic acid decarboxylase, and insulinoma associated-2 autoantibodies (IAA, GAD65, and IA-2) are the autoantibodies that have been associated most clearly with the development of T1D. |
| 2261 | 16295523 | The autoantigens of Type 1A diabetes may be divided into subgroups based on their tissue distributions: Beta-cell-specific antigens like insulin, insulin derivatives, and IGRP (Islet-specific Glucose-6-phosphatase catalytic subunit Related Peptide); neurendocrine antigens such as carboxypeptidase H, insulinoma-associated antigen (IA-2), glutamic acid decarboxylase (GAD65), and carboxypeptidase E; and those expressed ubiquitously like heat shock protein 60 (a putative autoantigen for type 1 diabetes). |
| 2262 | 16301686 | Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients. |
| 2263 | 16301686 | Autoantibodies to the 65-kDa isoform of glutamate decarboxylase GAD65 (GAD65Ab) are strong candidates for a pathological role in Stiff-Person syndrome (SPS). |
| 2264 | 16301686 | Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients. |
| 2265 | 16301686 | Autoantibodies to the 65-kDa isoform of glutamate decarboxylase GAD65 (GAD65Ab) are strong candidates for a pathological role in Stiff-Person syndrome (SPS). |
| 2266 | 16380228 | Insulin, GAD65, and IA-2 autoantibodies and leptin levels were measured in relatives of T1DM patients and in control subjects. |
| 2267 | 16380476 | Coexpression of CD25 and OX40 (CD134) receptors delineates autoreactive T-cells in type 1 diabetes. |
| 2268 | 16380476 | We used fluorescence-activated cell sorter analysis to study surface marker expression on T-cell lines specific for two major type 1 diabetes autoantigens, GAD65 and proinsulin. |
| 2269 | 16380476 | The autoreactive T-cells of patients could be distinguished from those of control subjects by their coexpression of CD25 and CD134. |
| 2270 | 16380476 | Autoantigen-specific T-cells that recognized multiple GAD65- and preproinsulin-derived peptides and coexpressed CD25(+)CD134(+) were confined to patients (n = 32) and pre-diabetic probands (n = 5). |
| 2271 | 16380476 | Autoantigen-reactive T-cells in control subjects (n = 21) were CD25(+)CD134(-) and recognized fewer autoantigen-derived peptides. |
| 2272 | 16380476 | Insulin therapy did not induce CD25(+)CD134(+) T-cells in type 2 diabetic patients. |
| 2273 | 16380476 | Coexpression of CD25 and OX40 (CD134) receptors delineates autoreactive T-cells in type 1 diabetes. |
| 2274 | 16380476 | We used fluorescence-activated cell sorter analysis to study surface marker expression on T-cell lines specific for two major type 1 diabetes autoantigens, GAD65 and proinsulin. |
| 2275 | 16380476 | The autoreactive T-cells of patients could be distinguished from those of control subjects by their coexpression of CD25 and CD134. |
| 2276 | 16380476 | Autoantigen-specific T-cells that recognized multiple GAD65- and preproinsulin-derived peptides and coexpressed CD25(+)CD134(+) were confined to patients (n = 32) and pre-diabetic probands (n = 5). |
| 2277 | 16380476 | Autoantigen-reactive T-cells in control subjects (n = 21) were CD25(+)CD134(-) and recognized fewer autoantigen-derived peptides. |
| 2278 | 16380476 | Insulin therapy did not induce CD25(+)CD134(+) T-cells in type 2 diabetic patients. |
| 2279 | 16390386 | Serum obtained at the time of enrollment was assayed for ICAs, glutamic acid decarboxylase (GAD)65, insulin A (IA)-2 AA, and insulin AAs (IAAs). |
| 2280 | 16390386 | In FDRs who had ICAs in addition to GAD65 and IA-2 AAs, the cumulative risk of developing insulin-requiring diabetes was 80% at 6.7 yr of follow-up, whereas this risk in those with GAD65 and IA-2 AAs without ICAs was only 14% at 10 yr of follow-up (log rank: P < 0.00001). |
| 2281 | 16390386 | Cox regression analysis showed that diabetes risk was significantly associated with the presence of ICAs in both subjects with low titer and high titer GAD65 and IA-2 AAs. |
| 2282 | 16390386 | The addition of IAAs in GAD65 and IA-2 AA-positive relatives did not increase the cumulative risk for conversion to insulin-treated diabetes. |
| 2283 | 16390386 | We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials. |
| 2284 | 16390386 | Serum obtained at the time of enrollment was assayed for ICAs, glutamic acid decarboxylase (GAD)65, insulin A (IA)-2 AA, and insulin AAs (IAAs). |
| 2285 | 16390386 | In FDRs who had ICAs in addition to GAD65 and IA-2 AAs, the cumulative risk of developing insulin-requiring diabetes was 80% at 6.7 yr of follow-up, whereas this risk in those with GAD65 and IA-2 AAs without ICAs was only 14% at 10 yr of follow-up (log rank: P < 0.00001). |
| 2286 | 16390386 | Cox regression analysis showed that diabetes risk was significantly associated with the presence of ICAs in both subjects with low titer and high titer GAD65 and IA-2 AAs. |
| 2287 | 16390386 | The addition of IAAs in GAD65 and IA-2 AA-positive relatives did not increase the cumulative risk for conversion to insulin-treated diabetes. |
| 2288 | 16390386 | We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials. |
| 2289 | 16390386 | Serum obtained at the time of enrollment was assayed for ICAs, glutamic acid decarboxylase (GAD)65, insulin A (IA)-2 AA, and insulin AAs (IAAs). |
| 2290 | 16390386 | In FDRs who had ICAs in addition to GAD65 and IA-2 AAs, the cumulative risk of developing insulin-requiring diabetes was 80% at 6.7 yr of follow-up, whereas this risk in those with GAD65 and IA-2 AAs without ICAs was only 14% at 10 yr of follow-up (log rank: P < 0.00001). |
| 2291 | 16390386 | Cox regression analysis showed that diabetes risk was significantly associated with the presence of ICAs in both subjects with low titer and high titer GAD65 and IA-2 AAs. |
| 2292 | 16390386 | The addition of IAAs in GAD65 and IA-2 AA-positive relatives did not increase the cumulative risk for conversion to insulin-treated diabetes. |
| 2293 | 16390386 | We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials. |
| 2294 | 16390386 | Serum obtained at the time of enrollment was assayed for ICAs, glutamic acid decarboxylase (GAD)65, insulin A (IA)-2 AA, and insulin AAs (IAAs). |
| 2295 | 16390386 | In FDRs who had ICAs in addition to GAD65 and IA-2 AAs, the cumulative risk of developing insulin-requiring diabetes was 80% at 6.7 yr of follow-up, whereas this risk in those with GAD65 and IA-2 AAs without ICAs was only 14% at 10 yr of follow-up (log rank: P < 0.00001). |
| 2296 | 16390386 | Cox regression analysis showed that diabetes risk was significantly associated with the presence of ICAs in both subjects with low titer and high titer GAD65 and IA-2 AAs. |
| 2297 | 16390386 | The addition of IAAs in GAD65 and IA-2 AA-positive relatives did not increase the cumulative risk for conversion to insulin-treated diabetes. |
| 2298 | 16390386 | We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials. |
| 2299 | 16442659 | Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes. |
| 2300 | 16442659 | We analyzed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase like IA-2 (IA-2A) as well as risk-associated polymorphisms of HLA, insulin and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) genes. |
| 2301 | 16442659 | The differences remained even when the patients were matched for HLA, insulin and CTLA-4 risk genotypes. |
| 2302 | 16442659 | Our results suggest that autoimmune process against insulin and GAD(65) is more common at diagnosis in children in areas with high incidence of type 1 diabetes (T1D), independent of genetic risk markers. |
| 2303 | 16442659 | Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes. |
| 2304 | 16442659 | We analyzed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase like IA-2 (IA-2A) as well as risk-associated polymorphisms of HLA, insulin and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) genes. |
| 2305 | 16442659 | The differences remained even when the patients were matched for HLA, insulin and CTLA-4 risk genotypes. |
| 2306 | 16442659 | Our results suggest that autoimmune process against insulin and GAD(65) is more common at diagnosis in children in areas with high incidence of type 1 diabetes (T1D), independent of genetic risk markers. |
| 2307 | 16461938 | Since the role that GABA plays in the islet and the mechanisms whereby the two major GAD isoforms (GAD65 and GAD67) function as diabetes-associated autoantigens are unknown, continued characterization of the islet GAD-GABA system is important. |
| 2308 | 16461938 | V52 may be better adapted than V57 to the unique rat alpha cell GAD-GABA system, which lacks GAD65 and in which VIAAT traffics to secretory granules rather than just to synaptic microvesicles. |
| 2309 | 16461938 | Since the role that GABA plays in the islet and the mechanisms whereby the two major GAD isoforms (GAD65 and GAD67) function as diabetes-associated autoantigens are unknown, continued characterization of the islet GAD-GABA system is important. |
| 2310 | 16461938 | V52 may be better adapted than V57 to the unique rat alpha cell GAD-GABA system, which lacks GAD65 and in which VIAAT traffics to secretory granules rather than just to synaptic microvesicles. |
| 2311 | 16573556 | Glutamate decarboxylase (GAD), which has two isoforms, GAD65, and GAD67, is responsible for synthesis of the major inhibitory neurotransmitter, gamma-aminobutyric acid. |
| 2312 | 16573556 | Almost all GFP-positive cells were positive for major histocompatibility complex (MHC) class II antigen staining and were positive for both cytokeratin and Ulex Europaeus Agglutinin I, markers of medullary thymic epithelial cells, but were negative for CD11c, Gr-1, and CD45, markers of dendritic cells, macrophages, and B-lymphocytes, respectively. |
| 2313 | 16704296 | Using the sensitive enzyme-linked immunospot (ELISPOT) technique to distinguish Th1-like from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was analyzed from PBMCs spontaneously and after in vitro stimulation with the diabetes-associated autoantigens, glutamic acid decarboxylase 65 (GAD65, protein and peptide, aa 247-279), recombinant tyrosine phosphatase (IA-2), and heat shock protein (HSP, aa 437-460). |
| 2314 | 16704296 | Secretion of IFN-gamma and the IFN-gamma/IL-4 ratio, induced by autoantigens, decreased in individuals developing T1D (p < 0.05), whereas nondiabetic individuals showed an increased IL-4 response (p < 0.05). |
| 2315 | 16790365 | However, in this study, we demonstrate protection against disease by covaccination with a mutant B7-1 molecule (B7-1wa) that binds the negative T cell regulator CTLA-4 (CD152), but not CD28. |
| 2316 | 16790365 | In vitro, the T cells of covaccinated mice had negative responses to both insulin and GAD65, and this was restored by adding blocking antibodies to transforming growth factor beta1 (TGF-beta1), suggesting a role for this cytokine. |
| 2317 | 16790365 | Furthermore, vaccinated mice had increased numbers of T cells with Tr-associated markers, such as CTLA-4, Foxp3, and membrane-bound TGF-beta1. |
| 2318 | 16972881 | Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. |
| 2319 | 16972881 | To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. |
| 2320 | 16972881 | JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. |
| 2321 | 16972881 | Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. |
| 2322 | 16972881 | Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65. |
| 2323 | 16972881 | Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. |
| 2324 | 16972881 | To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. |
| 2325 | 16972881 | JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. |
| 2326 | 16972881 | Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. |
| 2327 | 16972881 | Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65. |
| 2328 | 16972881 | Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. |
| 2329 | 16972881 | To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. |
| 2330 | 16972881 | JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. |
| 2331 | 16972881 | Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. |
| 2332 | 16972881 | Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65. |
| 2333 | 16979383 | We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. |
| 2334 | 16979383 | Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. |
| 2335 | 16979383 | Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. |
| 2336 | 16979383 | We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. |
| 2337 | 16979383 | Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. |
| 2338 | 16979383 | Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. |
| 2339 | 17130492 | A panel of human GAD (hGAD65)-specific CD4 T-cell lines and hybridomas was generated to serve as detection reagents for evaluating the peptide occupancy of DQ8 and DR4. |
| 2340 | 17130547 | Diabetes incidence in recipients of unpulsed iDC was comparable to unmanipulated animals ( approximately 80%), whereas GAD65(78-97) pulsed iDC recipients were protected from the disease (P = 0.05). |
| 2341 | 17130557 | Most T1D patients' sera contain two distinct glutamic acid decarboxylase (GAD) antibody specificities, of which one targets an epitope region in the middle-third of GAD65 (amino acids 221-359) and the other targets the carboxy-third of GAD65 (amino acids 453-569). |
| 2342 | 17130557 | Using five chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of antibodies from 127 T1D patients with and without autoimmune thyroid diseases (ATD). |
| 2343 | 17130557 | Those with GAD65 autoantibodies reacting with both middle- and carboxy-third had less ATD. |
| 2344 | 17130557 | Of 22 (23%) patients with ATD, 5 compared to 29 of 47 (62%) T1D patients without ATD had GAD65 autoantibodies reacting with both middle- and carboxy-third (relative risk = 0.2, P < 0.01). |
| 2345 | 17130557 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in ATD and T1D, and expression of antibodies to middle- and carboxy-third at the same time is a feature specific to T1D. |
| 2346 | 17130557 | Most T1D patients' sera contain two distinct glutamic acid decarboxylase (GAD) antibody specificities, of which one targets an epitope region in the middle-third of GAD65 (amino acids 221-359) and the other targets the carboxy-third of GAD65 (amino acids 453-569). |
| 2347 | 17130557 | Using five chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of antibodies from 127 T1D patients with and without autoimmune thyroid diseases (ATD). |
| 2348 | 17130557 | Those with GAD65 autoantibodies reacting with both middle- and carboxy-third had less ATD. |
| 2349 | 17130557 | Of 22 (23%) patients with ATD, 5 compared to 29 of 47 (62%) T1D patients without ATD had GAD65 autoantibodies reacting with both middle- and carboxy-third (relative risk = 0.2, P < 0.01). |
| 2350 | 17130557 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in ATD and T1D, and expression of antibodies to middle- and carboxy-third at the same time is a feature specific to T1D. |
| 2351 | 17130557 | Most T1D patients' sera contain two distinct glutamic acid decarboxylase (GAD) antibody specificities, of which one targets an epitope region in the middle-third of GAD65 (amino acids 221-359) and the other targets the carboxy-third of GAD65 (amino acids 453-569). |
| 2352 | 17130557 | Using five chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of antibodies from 127 T1D patients with and without autoimmune thyroid diseases (ATD). |
| 2353 | 17130557 | Those with GAD65 autoantibodies reacting with both middle- and carboxy-third had less ATD. |
| 2354 | 17130557 | Of 22 (23%) patients with ATD, 5 compared to 29 of 47 (62%) T1D patients without ATD had GAD65 autoantibodies reacting with both middle- and carboxy-third (relative risk = 0.2, P < 0.01). |
| 2355 | 17130557 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in ATD and T1D, and expression of antibodies to middle- and carboxy-third at the same time is a feature specific to T1D. |
| 2356 | 17130557 | Most T1D patients' sera contain two distinct glutamic acid decarboxylase (GAD) antibody specificities, of which one targets an epitope region in the middle-third of GAD65 (amino acids 221-359) and the other targets the carboxy-third of GAD65 (amino acids 453-569). |
| 2357 | 17130557 | Using five chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of antibodies from 127 T1D patients with and without autoimmune thyroid diseases (ATD). |
| 2358 | 17130557 | Those with GAD65 autoantibodies reacting with both middle- and carboxy-third had less ATD. |
| 2359 | 17130557 | Of 22 (23%) patients with ATD, 5 compared to 29 of 47 (62%) T1D patients without ATD had GAD65 autoantibodies reacting with both middle- and carboxy-third (relative risk = 0.2, P < 0.01). |
| 2360 | 17130557 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in ATD and T1D, and expression of antibodies to middle- and carboxy-third at the same time is a feature specific to T1D. |
| 2361 | 17130557 | Most T1D patients' sera contain two distinct glutamic acid decarboxylase (GAD) antibody specificities, of which one targets an epitope region in the middle-third of GAD65 (amino acids 221-359) and the other targets the carboxy-third of GAD65 (amino acids 453-569). |
| 2362 | 17130557 | Using five chimeric GAD65/GAD67 proteins to maintain conformation-dependent epitopes of GAD65, we compared the humoral repertoire of antibodies from 127 T1D patients with and without autoimmune thyroid diseases (ATD). |
| 2363 | 17130557 | Those with GAD65 autoantibodies reacting with both middle- and carboxy-third had less ATD. |
| 2364 | 17130557 | Of 22 (23%) patients with ATD, 5 compared to 29 of 47 (62%) T1D patients without ATD had GAD65 autoantibodies reacting with both middle- and carboxy-third (relative risk = 0.2, P < 0.01). |
| 2365 | 17130557 | These results indicate that there are both similarities and differences in the humoral response to GAD65 in ATD and T1D, and expression of antibodies to middle- and carboxy-third at the same time is a feature specific to T1D. |
| 2366 | 17130560 | MHC class I chain-related gene-A is associated with IA2 and IAA but not GAD in Swedish type 1 diabetes mellitus. |
| 2367 | 17130560 | In type 1 diabetes mellitus (T1DM), the frequency of antibodies against insulin (IAA), glutamic acid decarboxylase-65 (GAD65), ICA512/IA2 (IA2), and islet cell antigens (ICA) vary with human leukocyte antigen (HLA) composition of the patient. |
| 2368 | 17130560 | IAA, IA2 autoantibodies, and ICA are increased in DQ8 positives; GAD65 antibodies are increased in DQ2 positives. |
| 2369 | 17130560 | MHC class I chain-related gene-A (MICA) is another genetic marker that has been proposed to be associated with T1DM. |
| 2370 | 17130560 | In this article, we looked at microsatellite polymorphism of MICA and its association with autoantibodies (IAA, IA2, and GAD65) in Swedish T1DM patients and if the association explains its importance in early events in autoimmune response. |
| 2371 | 17130560 | MHC class I chain-related gene-A is associated with IA2 and IAA but not GAD in Swedish type 1 diabetes mellitus. |
| 2372 | 17130560 | In type 1 diabetes mellitus (T1DM), the frequency of antibodies against insulin (IAA), glutamic acid decarboxylase-65 (GAD65), ICA512/IA2 (IA2), and islet cell antigens (ICA) vary with human leukocyte antigen (HLA) composition of the patient. |
| 2373 | 17130560 | IAA, IA2 autoantibodies, and ICA are increased in DQ8 positives; GAD65 antibodies are increased in DQ2 positives. |
| 2374 | 17130560 | MHC class I chain-related gene-A (MICA) is another genetic marker that has been proposed to be associated with T1DM. |
| 2375 | 17130560 | In this article, we looked at microsatellite polymorphism of MICA and its association with autoantibodies (IAA, IA2, and GAD65) in Swedish T1DM patients and if the association explains its importance in early events in autoimmune response. |
| 2376 | 17130560 | MHC class I chain-related gene-A is associated with IA2 and IAA but not GAD in Swedish type 1 diabetes mellitus. |
| 2377 | 17130560 | In type 1 diabetes mellitus (T1DM), the frequency of antibodies against insulin (IAA), glutamic acid decarboxylase-65 (GAD65), ICA512/IA2 (IA2), and islet cell antigens (ICA) vary with human leukocyte antigen (HLA) composition of the patient. |
| 2378 | 17130560 | IAA, IA2 autoantibodies, and ICA are increased in DQ8 positives; GAD65 antibodies are increased in DQ2 positives. |
| 2379 | 17130560 | MHC class I chain-related gene-A (MICA) is another genetic marker that has been proposed to be associated with T1DM. |
| 2380 | 17130560 | In this article, we looked at microsatellite polymorphism of MICA and its association with autoantibodies (IAA, IA2, and GAD65) in Swedish T1DM patients and if the association explains its importance in early events in autoimmune response. |
| 2381 | 17163450 | CD8+ suppressor-mediated regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65. |
| 2382 | 17163450 | It has been well demonstrated that CD4+ CD25+ regulatory T cells play a significant role in controlling the expansion of autoreactive T cells in the periphery. |
| 2383 | 17163450 | However, some healthy individuals exhibit measurable responses to self peptide even in the presence of CD4+ CD25+ regulatory cells. |
| 2384 | 17163450 | This article describes the regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65 (GAD65), an autoantigen implicated in type-1 diabetes, by autologous CD8+ suppressor T cells. |
| 2385 | 17163450 | In cells cultured from healthy individuals, the inclusion of autologous CD8+ T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4+ T cell responses to GAD65 peptide. |
| 2386 | 17163450 | Cell fractionation studies suggested that CD8+ suppressor T cells originate from the CD45RA+ CD27- population. |
| 2387 | 17163450 | The suppression of CD4+ T cell responses to GAD65 in healthy individuals raises the possibility that CD8+ suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population. |
| 2388 | 17163450 | CD8+ suppressor-mediated regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65. |
| 2389 | 17163450 | It has been well demonstrated that CD4+ CD25+ regulatory T cells play a significant role in controlling the expansion of autoreactive T cells in the periphery. |
| 2390 | 17163450 | However, some healthy individuals exhibit measurable responses to self peptide even in the presence of CD4+ CD25+ regulatory cells. |
| 2391 | 17163450 | This article describes the regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65 (GAD65), an autoantigen implicated in type-1 diabetes, by autologous CD8+ suppressor T cells. |
| 2392 | 17163450 | In cells cultured from healthy individuals, the inclusion of autologous CD8+ T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4+ T cell responses to GAD65 peptide. |
| 2393 | 17163450 | Cell fractionation studies suggested that CD8+ suppressor T cells originate from the CD45RA+ CD27- population. |
| 2394 | 17163450 | The suppression of CD4+ T cell responses to GAD65 in healthy individuals raises the possibility that CD8+ suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population. |
| 2395 | 17163450 | CD8+ suppressor-mediated regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65. |
| 2396 | 17163450 | It has been well demonstrated that CD4+ CD25+ regulatory T cells play a significant role in controlling the expansion of autoreactive T cells in the periphery. |
| 2397 | 17163450 | However, some healthy individuals exhibit measurable responses to self peptide even in the presence of CD4+ CD25+ regulatory cells. |
| 2398 | 17163450 | This article describes the regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65 (GAD65), an autoantigen implicated in type-1 diabetes, by autologous CD8+ suppressor T cells. |
| 2399 | 17163450 | In cells cultured from healthy individuals, the inclusion of autologous CD8+ T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4+ T cell responses to GAD65 peptide. |
| 2400 | 17163450 | Cell fractionation studies suggested that CD8+ suppressor T cells originate from the CD45RA+ CD27- population. |
| 2401 | 17163450 | The suppression of CD4+ T cell responses to GAD65 in healthy individuals raises the possibility that CD8+ suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population. |
| 2402 | 17210161 | The obtained time-resolved fluorescence (TRF) is directly proportional to the concentration of GAD65 over a large measuring range (0.1 to >100 ng/mL). |
| 2403 | 17259239 | Time-resolved immunofluorometric dual-label assay for simultaneous detection of autoantibodies to GAD65 and IA-2 in children with type 1 diabetes. |
| 2404 | 17317763 | To define the parameters influencing the efficacy of antigen-specific immunotherapy once diabetes is established, plasmid DNA (pDNA) vaccination was used to suppress autoimmune-mediated destruction of syngeneic islet grafts in diabetic NOD recipients. pDNAs encoding a glutamic acid decarboxylase 65 (GAD65)-Ig molecule (pGAD65), interleukin (IL)-4 (pIL4), and IL-10 (pIL10) significantly delayed the onset of recurrent diabetes compared with pGAD65+pIL10-vaccinated recipients. |
| 2405 | 17317763 | Despite differences in efficacy, a similar frequency of GAD65-specific CD4(+) T-cells secreting IL-4, IL-10, or interferon-gamma were detected in mice treated with pGAD65+pIL4+pIL10 and pGAD65+pIL10. |
| 2406 | 17317763 | However, the frequency of FoxP3-expressing CD4(+)CD25(+)CD62L(hi) T-cells was increased in the renal and pancreatic lymph nodes of diabetic recipients vaccinated with pGAD65+pIL4+pIL10. |
| 2407 | 17317763 | These immunoregulatory CD4(+)CD25(+) T-cells (CD4(+)CD25(+) Treg) exhibited enhanced in vivo and in vitro suppressor activity that partially was transforming growth factor-beta dependent. |
| 2408 | 17317763 | Furthermore, duration of islet graft protection in pGAD65+pIL4+pIL10-vaccinated diabetic recipients correlated with the persistence of CD4(+)CD25(+) Treg. |
| 2409 | 17317763 | These data demonstrate that the frequency and maintenance of FoxP3-expressing CD4(+)CD25(+) Treg influence antigen-induced suppression of ongoing beta-cell autoimmunity in diabetic recipients. |
| 2410 | 17317763 | To define the parameters influencing the efficacy of antigen-specific immunotherapy once diabetes is established, plasmid DNA (pDNA) vaccination was used to suppress autoimmune-mediated destruction of syngeneic islet grafts in diabetic NOD recipients. pDNAs encoding a glutamic acid decarboxylase 65 (GAD65)-Ig molecule (pGAD65), interleukin (IL)-4 (pIL4), and IL-10 (pIL10) significantly delayed the onset of recurrent diabetes compared with pGAD65+pIL10-vaccinated recipients. |
| 2411 | 17317763 | Despite differences in efficacy, a similar frequency of GAD65-specific CD4(+) T-cells secreting IL-4, IL-10, or interferon-gamma were detected in mice treated with pGAD65+pIL4+pIL10 and pGAD65+pIL10. |
| 2412 | 17317763 | However, the frequency of FoxP3-expressing CD4(+)CD25(+)CD62L(hi) T-cells was increased in the renal and pancreatic lymph nodes of diabetic recipients vaccinated with pGAD65+pIL4+pIL10. |
| 2413 | 17317763 | These immunoregulatory CD4(+)CD25(+) T-cells (CD4(+)CD25(+) Treg) exhibited enhanced in vivo and in vitro suppressor activity that partially was transforming growth factor-beta dependent. |
| 2414 | 17317763 | Furthermore, duration of islet graft protection in pGAD65+pIL4+pIL10-vaccinated diabetic recipients correlated with the persistence of CD4(+)CD25(+) Treg. |
| 2415 | 17317763 | These data demonstrate that the frequency and maintenance of FoxP3-expressing CD4(+)CD25(+) Treg influence antigen-induced suppression of ongoing beta-cell autoimmunity in diabetic recipients. |
| 2416 | 17376837 | Glutamic acid decarboxylase (GAD65) and insulin are implicated as target antigens in the pathogenesis of human diabetes through correlative measurements of humoral and cellular reactivity to them in diabetics and at-risk diabetic individuals. |
| 2417 | 17479437 | Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels. |
| 2418 | 17479437 | T1D patients and control subjects from the Swedish Childhood Diabetes Registry and the Swedish Diabetes Incidence Study registry were genotyped for two GCLC promoter polymorphisms; the GCLC -129 C to T single nucleotide polymorphism (GCLC -129 SNP) and the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR). |
| 2419 | 17479437 | In addition, T1D patients with an age-at-onset of 14-35 years possess the GCLC TNR 7/8 genotype at a lower frequency than the control subjects (OR, 0.33, 95% CI, 0.13-0.82). |
| 2420 | 17479437 | The GCLC -129 SNP and GCLC TNR appear to be in linkage disequilibrium (p-value<0.0001). |
| 2421 | 17558682 | She was diagnosed with: (1) type 1 diabetes, with hyperglycemia, impaired insulin secretion, and positive autoantibodies for GAD-65 and IA-2; (2) autoimmune thyroiditis, with hypothyroidism, positive anti-microsomal and antithyroglobulin antibodies; and (3) PCOS, with hyperandrogenic signs that had developed 5 years earlier, amenorrhea for the previous 6 months, and characteristic multiple microcystic appearance of both ovaries on ultrasonography. |
| 2422 | 17666094 | The use of biotin-conjugated antibodies and streptavidin Sepharose are used commonly in immunoprecipitation assays (IPA) based on (125)I- or (35)S-labelled antigens to capture IgG subclasses directed against IA-2 or GAD(65). |
| 2423 | 17947651 | In this study, a CSFE dilution assay was used to detect glutamic acid decarboxylase 65 (GAD65)- and insulin-responsive T cells and HLA-0201*-GAD65(114-122) pentamers were used to detect CD8(+) GAD-responsive T cells in memory CD45RO(+) and naive CD45RO(-) cell populations from patients with type 1 diabetes and healthy control subjects. |
| 2424 | 17947651 | CD4(+) and CD8(+) T cells specific for GAD65 and insulin were present in patients with type 1 diabetes and control subjects. |
| 2425 | 17947651 | Within the naive CD45RO(-) cells, CD4(+) and CD8(+) T cell responses were similar between patients and controls. |
| 2426 | 17947651 | Within the memory CD45RO(+) cells, CD4(+) T cell responses against whole GAD65 and insulin and HLA-0201*-GAD65(114-122) pentamer-positive CD8(+) T cells were found in patients with type 1 diabetes, but not in control subjects (p < 0.05 for all). |
| 2427 | 17947651 | In this study, a CSFE dilution assay was used to detect glutamic acid decarboxylase 65 (GAD65)- and insulin-responsive T cells and HLA-0201*-GAD65(114-122) pentamers were used to detect CD8(+) GAD-responsive T cells in memory CD45RO(+) and naive CD45RO(-) cell populations from patients with type 1 diabetes and healthy control subjects. |
| 2428 | 17947651 | CD4(+) and CD8(+) T cells specific for GAD65 and insulin were present in patients with type 1 diabetes and control subjects. |
| 2429 | 17947651 | Within the naive CD45RO(-) cells, CD4(+) and CD8(+) T cell responses were similar between patients and controls. |
| 2430 | 17947651 | Within the memory CD45RO(+) cells, CD4(+) T cell responses against whole GAD65 and insulin and HLA-0201*-GAD65(114-122) pentamer-positive CD8(+) T cells were found in patients with type 1 diabetes, but not in control subjects (p < 0.05 for all). |
| 2431 | 17949947 | The source of TcR was a CD4(+) T(H)1(+) T-cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. |
| 2432 | 17949947 | The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. |
| 2433 | 17949947 | T cells containing the GAD65/67 (555-567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1% of CD4(+) T cells in Rag2 sufficient mice. |
| 2434 | 17949947 | Upon in vitro stimulation, GAD65/67 555-567 responsive T cells secrete interferon-gamma, minimal interleukin (IL)-2 and tumor necrosis factor-alpha, and no IL-4, IL-5, IL-10, or IL-17, consistent with a T(H)1 profile. |
| 2435 | 17949947 | These data demonstrate that CD4(+) T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta-cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. |
| 2436 | 17949947 | The source of TcR was a CD4(+) T(H)1(+) T-cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. |
| 2437 | 17949947 | The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. |
| 2438 | 17949947 | T cells containing the GAD65/67 (555-567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1% of CD4(+) T cells in Rag2 sufficient mice. |
| 2439 | 17949947 | Upon in vitro stimulation, GAD65/67 555-567 responsive T cells secrete interferon-gamma, minimal interleukin (IL)-2 and tumor necrosis factor-alpha, and no IL-4, IL-5, IL-10, or IL-17, consistent with a T(H)1 profile. |
| 2440 | 17949947 | These data demonstrate that CD4(+) T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta-cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. |
| 2441 | 17949947 | The source of TcR was a CD4(+) T(H)1(+) T-cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. |
| 2442 | 17949947 | The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. |
| 2443 | 17949947 | T cells containing the GAD65/67 (555-567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1% of CD4(+) T cells in Rag2 sufficient mice. |
| 2444 | 17949947 | Upon in vitro stimulation, GAD65/67 555-567 responsive T cells secrete interferon-gamma, minimal interleukin (IL)-2 and tumor necrosis factor-alpha, and no IL-4, IL-5, IL-10, or IL-17, consistent with a T(H)1 profile. |
| 2445 | 17949947 | These data demonstrate that CD4(+) T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta-cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. |
| 2446 | 17950950 | Autoantibodies to GAD65 or IA-2 were negative throughout the clinical course in two cases, but transiently positive in one case. |
| 2447 | 18300057 | The two possibilities to explain the pathogenic basis of stiff-person syndrome (SPS) are intrathecal sensitization of GAD65-reactive CD4+T cells and synthesis of GAD65-specific autoantibodies within the CNS [Rakocevic et al., Arch. |
| 2448 | 18514483 | Conformational epitopes of GAD65 have been mapped using human monoclonal antibodies to GAD65 and GAD mutated by GAD65/67 sequence exchanges or point mutations, but these studies have been limited by a lack of structural information. |
| 2449 | 18549445 | The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-beta are associated with regulatory T cell activity. |
| 2450 | 18549445 | CTLA-4, sCTLA-4, FoxP3 and TGF-beta mRNA transcription was quantified. |
| 2451 | 18549445 | Placebo individuals increased in spontaneous CTLA-4 mRNA (P < 0.05) but decreased in expression after stimulation with GAD(65)-peptide (P < 0.05) and PHA (P < 0.05). |
| 2452 | 18549445 | Spontaneous TGF-beta (P < 0.05) increased whereas PHA- (P < 0.01) and GAD(65)-peptide (P < 0.01)-induced TGF-beta expression decreased in the placebo group, whereas it was maintained in the treated group. |
| 2453 | 18549445 | Without intervention, expression of CTLA-4 and TGF-beta, stimulated with PHA and GAD(65) peptide, decreased with time, with a parallel reduction of GAD(65)-peptide and PHA-stimulated TGF-beta expression. |
| 2454 | 18761006 | PBMC were cultured before and after cryopreservation either with GAD(65) or PHA. |
| 2455 | 18761006 | Secretion of cytokines (IL-5, -6, -10, -12, -13 -17, IFN-gamma and TNF-alpha) and chemokines (IP-10, MCP-1, MIP-1alpha, MIP-1beta and RANTES) was analysed in cell supernatants using multiplex fluorochrome technique (Luminex). |
| 2456 | 18761006 | Expression of FOXP3 and TGF-beta mRNA was detected by multiplex real-time RT-PCR. |
| 2457 | 18761006 | Increased spontaneous secretion of IL-6, -10, -12, -13, IFN-gamma and MCP-1, and mRNA expression of FOXP3 and TGF-beta, was detected after cryopreservation. |
| 2458 | 18761006 | Stimulation with GAD(65) induced higher levels of IL-6, IFN-gamma, TNF-alpha and MIP-1alpha, whereas lower secretion was found for IL-10 and IL-13 in cryopreserved PBMC. |
| 2459 | 18761006 | Stimulation with PHA induced lower secretion of IP-10, MCP-1 and RANTES and FOXP3 mRNA expression after cryopreservation. |
| 2460 | 18761006 | PBMC were cultured before and after cryopreservation either with GAD(65) or PHA. |
| 2461 | 18761006 | Secretion of cytokines (IL-5, -6, -10, -12, -13 -17, IFN-gamma and TNF-alpha) and chemokines (IP-10, MCP-1, MIP-1alpha, MIP-1beta and RANTES) was analysed in cell supernatants using multiplex fluorochrome technique (Luminex). |
| 2462 | 18761006 | Expression of FOXP3 and TGF-beta mRNA was detected by multiplex real-time RT-PCR. |
| 2463 | 18761006 | Increased spontaneous secretion of IL-6, -10, -12, -13, IFN-gamma and MCP-1, and mRNA expression of FOXP3 and TGF-beta, was detected after cryopreservation. |
| 2464 | 18761006 | Stimulation with GAD(65) induced higher levels of IL-6, IFN-gamma, TNF-alpha and MIP-1alpha, whereas lower secretion was found for IL-10 and IL-13 in cryopreserved PBMC. |
| 2465 | 18761006 | Stimulation with PHA induced lower secretion of IP-10, MCP-1 and RANTES and FOXP3 mRNA expression after cryopreservation. |
| 2466 | 19085183 | High titre of autoantibodies against GAD(65) (GAD(65)Abs) have also been detected in some other autoimmune diseases. |
| 2467 | 19085183 | In search of a potential immunological marker of type 1 diabetes, in vitro GAD(65) was modified by hydroxyl radical followed by the study of structural and conformational perturbed protein by different spectroscopic techniques (UV, fluorescence and CD) and thermal denaturation profile. |
| 2468 | 19085183 | Binding studies of circulating autoantibodies from diabetic groups (type 1 and type 2) with native and reactive oxygen species (ROS) modified GAD(65), exhibited high recognition of type 1 diabetic serum autoantibodies with modified antigen (p < 0.001) over unmodified GAD(65). |
| 2469 | 19085183 | Relative affinity of ROS-GAD(65)Abs for modified and native GAD(65) was in the order of 1.56 x 10(- 6) and 2.72 x 10(- 7) M, as calculated by Langmuir plot. |
| 2470 | 19085183 | In coherence, ROS oxidation of GAD(65) causes conformational perturbation, generating highly immunogenic unique neoepitopes that may be one of the factors in antigen-driven induction of type 1 diabetes autoantibodies that can serve as a potential marker in early diagnosis/prognosis of the disease. |
| 2471 | 19085183 | High titre of autoantibodies against GAD(65) (GAD(65)Abs) have also been detected in some other autoimmune diseases. |
| 2472 | 19085183 | In search of a potential immunological marker of type 1 diabetes, in vitro GAD(65) was modified by hydroxyl radical followed by the study of structural and conformational perturbed protein by different spectroscopic techniques (UV, fluorescence and CD) and thermal denaturation profile. |
| 2473 | 19085183 | Binding studies of circulating autoantibodies from diabetic groups (type 1 and type 2) with native and reactive oxygen species (ROS) modified GAD(65), exhibited high recognition of type 1 diabetic serum autoantibodies with modified antigen (p < 0.001) over unmodified GAD(65). |
| 2474 | 19085183 | Relative affinity of ROS-GAD(65)Abs for modified and native GAD(65) was in the order of 1.56 x 10(- 6) and 2.72 x 10(- 7) M, as calculated by Langmuir plot. |
| 2475 | 19085183 | In coherence, ROS oxidation of GAD(65) causes conformational perturbation, generating highly immunogenic unique neoepitopes that may be one of the factors in antigen-driven induction of type 1 diabetes autoantibodies that can serve as a potential marker in early diagnosis/prognosis of the disease. |
| 2476 | 19085183 | High titre of autoantibodies against GAD(65) (GAD(65)Abs) have also been detected in some other autoimmune diseases. |
| 2477 | 19085183 | In search of a potential immunological marker of type 1 diabetes, in vitro GAD(65) was modified by hydroxyl radical followed by the study of structural and conformational perturbed protein by different spectroscopic techniques (UV, fluorescence and CD) and thermal denaturation profile. |
| 2478 | 19085183 | Binding studies of circulating autoantibodies from diabetic groups (type 1 and type 2) with native and reactive oxygen species (ROS) modified GAD(65), exhibited high recognition of type 1 diabetic serum autoantibodies with modified antigen (p < 0.001) over unmodified GAD(65). |
| 2479 | 19085183 | Relative affinity of ROS-GAD(65)Abs for modified and native GAD(65) was in the order of 1.56 x 10(- 6) and 2.72 x 10(- 7) M, as calculated by Langmuir plot. |
| 2480 | 19085183 | In coherence, ROS oxidation of GAD(65) causes conformational perturbation, generating highly immunogenic unique neoepitopes that may be one of the factors in antigen-driven induction of type 1 diabetes autoantibodies that can serve as a potential marker in early diagnosis/prognosis of the disease. |
| 2481 | 19085183 | High titre of autoantibodies against GAD(65) (GAD(65)Abs) have also been detected in some other autoimmune diseases. |
| 2482 | 19085183 | In search of a potential immunological marker of type 1 diabetes, in vitro GAD(65) was modified by hydroxyl radical followed by the study of structural and conformational perturbed protein by different spectroscopic techniques (UV, fluorescence and CD) and thermal denaturation profile. |
| 2483 | 19085183 | Binding studies of circulating autoantibodies from diabetic groups (type 1 and type 2) with native and reactive oxygen species (ROS) modified GAD(65), exhibited high recognition of type 1 diabetic serum autoantibodies with modified antigen (p < 0.001) over unmodified GAD(65). |
| 2484 | 19085183 | Relative affinity of ROS-GAD(65)Abs for modified and native GAD(65) was in the order of 1.56 x 10(- 6) and 2.72 x 10(- 7) M, as calculated by Langmuir plot. |
| 2485 | 19085183 | In coherence, ROS oxidation of GAD(65) causes conformational perturbation, generating highly immunogenic unique neoepitopes that may be one of the factors in antigen-driven induction of type 1 diabetes autoantibodies that can serve as a potential marker in early diagnosis/prognosis of the disease. |
| 2486 | 19085183 | High titre of autoantibodies against GAD(65) (GAD(65)Abs) have also been detected in some other autoimmune diseases. |
| 2487 | 19085183 | In search of a potential immunological marker of type 1 diabetes, in vitro GAD(65) was modified by hydroxyl radical followed by the study of structural and conformational perturbed protein by different spectroscopic techniques (UV, fluorescence and CD) and thermal denaturation profile. |
| 2488 | 19085183 | Binding studies of circulating autoantibodies from diabetic groups (type 1 and type 2) with native and reactive oxygen species (ROS) modified GAD(65), exhibited high recognition of type 1 diabetic serum autoantibodies with modified antigen (p < 0.001) over unmodified GAD(65). |
| 2489 | 19085183 | Relative affinity of ROS-GAD(65)Abs for modified and native GAD(65) was in the order of 1.56 x 10(- 6) and 2.72 x 10(- 7) M, as calculated by Langmuir plot. |
| 2490 | 19085183 | In coherence, ROS oxidation of GAD(65) causes conformational perturbation, generating highly immunogenic unique neoepitopes that may be one of the factors in antigen-driven induction of type 1 diabetes autoantibodies that can serve as a potential marker in early diagnosis/prognosis of the disease. |
| 2491 | 19111163 | GAD65 autoantibodies predict conversion to insulin dependence when present in patients classified with type 2 diabetes nowadays more often referred to as patients with latent autoimmune diabetes in the adult (LADA) or type 1,5 diabetes. |
| 2492 | 19111163 | Analyses of T cells with HLA DRB1 0401-tetramers with GAD65-specific peptides as well as of anti-idiotypic GAD65 autoantibodies suggest that GAD65 autoreactivity is common. |
| 2493 | 19111163 | GAD65 autoantibodies predict conversion to insulin dependence when present in patients classified with type 2 diabetes nowadays more often referred to as patients with latent autoimmune diabetes in the adult (LADA) or type 1,5 diabetes. |
| 2494 | 19111163 | Analyses of T cells with HLA DRB1 0401-tetramers with GAD65-specific peptides as well as of anti-idiotypic GAD65 autoantibodies suggest that GAD65 autoreactivity is common. |
| 2495 | 19120261 | Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. |
| 2496 | 19120303 | When compared with that of T2D, a higher proportion of patients with T1D were positive for GAD-65 and IA-2 antibodies, and this difference was statistically significant for GAD-65 antibodies. |
| 2497 | 19120319 | Stocks of the WHO islet cell antibody, GAD(65) antibody, and IA-2 antibody standard (NIBSC 97/550) are now very limited. |
| 2498 | 19120319 | We have therefore made and tested a series of control preparations in which human monoclonal autoantibodies to IA-2 and to GAD(65) were diluted in antibody-negative human serum to different concentrations. |
| 2499 | 19120319 | After reconstitution (with 1 mL of water) the controls were tested by (125)I-IA-2 immunoprecipitation assay (IPA), (125)I-GAD(65) IPA, GAD(65) Ab ELISA and IA-2 Ab ELISA (kits from RSR Ltd.) and for ICA by immunofluorescence test (IFT). |
| 2500 | 19120319 | DAC1 is particularly suitable as a control for the (125)I IA-2 IPA; DAC2 is suitable for the (125)I-GAD(65) IPA, GAD(65) Ab ELISA, and IA-2 Ab ELISA; and DAC3 is suitable for the ICA IFT. |
| 2501 | 19136037 | The effect of CTLA-4 allele and haplotype frequencies on the interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta(1) levels and the presence in serum of GAD65 and IA-2 autoantibodies at the onset of T1D was evaluated. |
| 2502 | 19136037 | On the other hand, higher ketoacidosis at onset, younger age at onset, and higher levels of tumor necrosis factor-alpha and interferon-gamma were observed in T1D patients carriers of G allele in comparison with the carriers of AA genotype. |
| 2503 | 19188044 | Several antigens such as insulin, glutamic acid decarboxylase (GAD) and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) are considered to take part in the autoimmune destructive process. |
| 2504 | 19188044 | Because the role of GAD in the disease process of type 1 diabetes is still controversial, we investigated the disease phenotype upon in vivo induction of whole GAD65 reactivity using a GAD65 homo knockout NOD splenocytes to NOD-scid transfer system. |
| 2505 | 19188044 | Splenocytes from recipients of KOT splenocytes produced IL-10 (/IFN-gamma) upon GAD65 stimulation, whereas those from recipients of WTT splenocytes did not. |
| 2506 | 19188044 | Several antigens such as insulin, glutamic acid decarboxylase (GAD) and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) are considered to take part in the autoimmune destructive process. |
| 2507 | 19188044 | Because the role of GAD in the disease process of type 1 diabetes is still controversial, we investigated the disease phenotype upon in vivo induction of whole GAD65 reactivity using a GAD65 homo knockout NOD splenocytes to NOD-scid transfer system. |
| 2508 | 19188044 | Splenocytes from recipients of KOT splenocytes produced IL-10 (/IFN-gamma) upon GAD65 stimulation, whereas those from recipients of WTT splenocytes did not. |
| 2509 | 19267332 | Administration of the isoform GAD65 can prevent autoimmune destruction of pancreatic beta cells in non-obese diabetic (NOD) mice and the subsequent need for exogenous insulin replacement. |
| 2510 | 19267332 | A double-blind randomized Phase II trial in 70 patients (10-18 years old) with recent-onset type 1 diabetes showed significant preservation of residual insulin secretion and a GAD-specific immune response, both humoral and cell-mediated, but no treatment-related adverse events. |
| 2511 | 19273071 | We have studied three possible ways that could modulate the processing and presentation of T cell determinants of a diabetes autoantigen, glutamic acid decarboxylase (GAD) 65, which could contribute to induction of GAD65-specific regulatory versus pathogenic T cells in type 1 diabetes (T1D): 1) enhanced presentation of subdominant/cryptic determinants to T cells that have not been well-tolerized, which may activate T cells of high affinity and high aggressiveness; 2) trimming or truncating flanking residues which may otherwise provide needed binding energy to determinants that activate regulatory cells, thus releasing autoaggressive T cells from suppression; 3) biochemical or chemical modifications of self antigens in an inflammatory environment or within activated antigen presenting cells (APC) which may convert a previously regulatory antigen or determinant into a disease-causing one that activates autoreactive T cells at a higher affinity. |
| 2512 | 19298606 | A medical history was recorded and a blood sample was analysed for autoantibodies against gliadin, transglutaminase, adrenal cortex, intrinsic factor, anti-thyroid peroxidase (anti-TPO) and glutamic-acid-decarboxylase 65 (GAD-65). |
| 2513 | 19465164 | For the past twenty years the type 1 diabetes autoantigen glutamic acid decarboxylase (65 kDa isoform; GAD65) has become a prototypic autoantigen, yielding a wealth of immunological and clinical insights. |
| 2514 | 19557295 | Autoimmunity to islet cell antigens like glutamic acid decarboxylase 65kD (GAD65) is associated with the destruction of insulin-producing beta-cells and progression to type 1 diabetes (T1D) in NOD mice and humans. |
| 2515 | 19557295 | Further, co-culture of GAD65(546-554)-specific CTL with the beta-cells leads to a reduction in insulin production and the induction of perforin-mediated cell death. |
| 2516 | 19557295 | Autoimmunity to islet cell antigens like glutamic acid decarboxylase 65kD (GAD65) is associated with the destruction of insulin-producing beta-cells and progression to type 1 diabetes (T1D) in NOD mice and humans. |
| 2517 | 19557295 | Further, co-culture of GAD65(546-554)-specific CTL with the beta-cells leads to a reduction in insulin production and the induction of perforin-mediated cell death. |
| 2518 | 19690518 | Efficacy was associated with an expansion of bystander suppressor regulatory T cells (Tregs) recognizing the C-terminal region of GAD65 and secreting interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma). |
| 2519 | 19690518 | In addition, we found that frequency and epitope specificity of GAD65-reactive CD4(+) T cells during antigen priming at diabetes onset and Tregs detected after CT correlated. |
| 2520 | 19690518 | Consequently, NOD mice harbored significantly lower levels of GAD65-reactive CD4(+) T cells than RIP-LCMV-GP before and after treatment. |
| 2521 | 19690518 | Efficacy was associated with an expansion of bystander suppressor regulatory T cells (Tregs) recognizing the C-terminal region of GAD65 and secreting interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma). |
| 2522 | 19690518 | In addition, we found that frequency and epitope specificity of GAD65-reactive CD4(+) T cells during antigen priming at diabetes onset and Tregs detected after CT correlated. |
| 2523 | 19690518 | Consequently, NOD mice harbored significantly lower levels of GAD65-reactive CD4(+) T cells than RIP-LCMV-GP before and after treatment. |
| 2524 | 19690518 | Efficacy was associated with an expansion of bystander suppressor regulatory T cells (Tregs) recognizing the C-terminal region of GAD65 and secreting interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma). |
| 2525 | 19690518 | In addition, we found that frequency and epitope specificity of GAD65-reactive CD4(+) T cells during antigen priming at diabetes onset and Tregs detected after CT correlated. |
| 2526 | 19690518 | Consequently, NOD mice harbored significantly lower levels of GAD65-reactive CD4(+) T cells than RIP-LCMV-GP before and after treatment. |
| 2527 | 19752238 | Furthermore, suppression of T1D was dependent on beta cell-specific IL-10-secreting CD4+ T cells, although the frequency of GAD65-specific FoxP3-expressing CD4+ T cells was also increased in sIA(g7)-pGAD65 dimer vaccinated NOD mice. |
| 2528 | 19768773 | Fifty diabetic patients and 30 controls with other autoimmune diseases underwent neurological examination and search for antibodies to gangliosides, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase (IA2). |
| 2529 | 19768773 | Disease duration was shorter in patients with antibodies to GAD(65) and IA2 and longer in neuropathic patients. |
| 2530 | 20029631 | Detection of GAD65 autoreactive T-cells by HLA class I tetramers in type 1 diabetic patients. |
| 2531 | 20029631 | We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. |
| 2532 | 20029631 | Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. |
| 2533 | 20029631 | Detection of GAD65 autoreactive T-cells by HLA class I tetramers in type 1 diabetic patients. |
| 2534 | 20029631 | We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. |
| 2535 | 20029631 | Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. |
| 2536 | 20029631 | Detection of GAD65 autoreactive T-cells by HLA class I tetramers in type 1 diabetic patients. |
| 2537 | 20029631 | We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. |
| 2538 | 20029631 | Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. |
| 2539 | 20083660 | Peptides in VP7, a major immunogenic protein of RV, have high sequence similarity to T cell epitope peptides in the islet autoantigens tyrosine phosphatase-like insulinoma Ag 2 (IA2) and glutamic acid decarboxylase 65 (GAD65). |
| 2540 | 20083660 | Peptides in RV and their sequence-similar counterparts in IA2 and GAD65 were assayed for binding to HLA molecules associated with type 1 diabetes and for the ability to elicit T cell proliferative responses in HLA-typed individuals. |
| 2541 | 20083660 | Peptides in RV-VP7, similar to T cell epitopes in IA2 and GAD65, bound strongly to HLA-DRB1*04 molecules that confer susceptibility to type 1 diabetes and were also T cell epitopes in humans at risk for type 1 diabetes. |
| 2542 | 20083660 | T cells expanded to the IA2 epitope could be restimulated to express IFN-gamma by the similar peptide in RV-VP7, and T cell clones generated to this RV-VP7 peptide cross-reacted with the IA2 epitope. |
| 2543 | 20083660 | Peptides in VP7, a major immunogenic protein of RV, have high sequence similarity to T cell epitope peptides in the islet autoantigens tyrosine phosphatase-like insulinoma Ag 2 (IA2) and glutamic acid decarboxylase 65 (GAD65). |
| 2544 | 20083660 | Peptides in RV and their sequence-similar counterparts in IA2 and GAD65 were assayed for binding to HLA molecules associated with type 1 diabetes and for the ability to elicit T cell proliferative responses in HLA-typed individuals. |
| 2545 | 20083660 | Peptides in RV-VP7, similar to T cell epitopes in IA2 and GAD65, bound strongly to HLA-DRB1*04 molecules that confer susceptibility to type 1 diabetes and were also T cell epitopes in humans at risk for type 1 diabetes. |
| 2546 | 20083660 | T cells expanded to the IA2 epitope could be restimulated to express IFN-gamma by the similar peptide in RV-VP7, and T cell clones generated to this RV-VP7 peptide cross-reacted with the IA2 epitope. |
| 2547 | 20083660 | Peptides in VP7, a major immunogenic protein of RV, have high sequence similarity to T cell epitope peptides in the islet autoantigens tyrosine phosphatase-like insulinoma Ag 2 (IA2) and glutamic acid decarboxylase 65 (GAD65). |
| 2548 | 20083660 | Peptides in RV and their sequence-similar counterparts in IA2 and GAD65 were assayed for binding to HLA molecules associated with type 1 diabetes and for the ability to elicit T cell proliferative responses in HLA-typed individuals. |
| 2549 | 20083660 | Peptides in RV-VP7, similar to T cell epitopes in IA2 and GAD65, bound strongly to HLA-DRB1*04 molecules that confer susceptibility to type 1 diabetes and were also T cell epitopes in humans at risk for type 1 diabetes. |
| 2550 | 20083660 | T cells expanded to the IA2 epitope could be restimulated to express IFN-gamma by the similar peptide in RV-VP7, and T cell clones generated to this RV-VP7 peptide cross-reacted with the IA2 epitope. |
| 2551 | 20086252 | Comparison of radioimmunoprecipitation with luciferase immunoprecipitation for autoantibodies to GAD65 and IA-2beta. |
| 2552 | 20348424 | High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. |
| 2553 | 20348424 | Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. |
| 2554 | 20348424 | In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. |
| 2555 | 20348424 | GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. |
| 2556 | 20348424 | In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. |
| 2557 | 20348424 | These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS. |
| 2558 | 20348424 | High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. |
| 2559 | 20348424 | Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. |
| 2560 | 20348424 | In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. |
| 2561 | 20348424 | GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. |
| 2562 | 20348424 | In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. |
| 2563 | 20348424 | These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS. |
| 2564 | 20348424 | High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. |
| 2565 | 20348424 | Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. |
| 2566 | 20348424 | In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. |
| 2567 | 20348424 | GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. |
| 2568 | 20348424 | In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. |
| 2569 | 20348424 | These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS. |
| 2570 | 20348424 | High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. |
| 2571 | 20348424 | Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. |
| 2572 | 20348424 | In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. |
| 2573 | 20348424 | GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. |
| 2574 | 20348424 | In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. |
| 2575 | 20348424 | These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS. |
| 2576 | 20348424 | High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. |
| 2577 | 20348424 | Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. |
| 2578 | 20348424 | In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. |
| 2579 | 20348424 | GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. |
| 2580 | 20348424 | In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. |
| 2581 | 20348424 | These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS. |
| 2582 | 20370569 | A low antigen dose selectively promotes expansion of high-avidity autoreactive T cells with distinct phenotypic characteristics: a study of human autoreactive CD4+T cells specific for GAD65. |
| 2583 | 20370569 | We addressed the question, how antigen dose shapes the diversity of CD4+ autoreactive T cells specific for glutamate decarboxylase 65 (GAD65) in a healthy HLA-DR*0404+ individual, with a persistent GAD65-specific T-cell response. |
| 2584 | 20370569 | CD4+T cells from this subject were stimulated with decreasing concentrations of the GAD65 555-567 (557I) peptide, and T-cell clones were derived from the tetramer-binding cell population. |
| 2585 | 20370569 | High IL-13 and IL-10 production by GAD65-reactive T cells suggests a more anti-inflammatory profile of this healthy individual underlying protection from T1D. |
| 2586 | 20370569 | A low antigen dose selectively promotes expansion of high-avidity autoreactive T cells with distinct phenotypic characteristics: a study of human autoreactive CD4+T cells specific for GAD65. |
| 2587 | 20370569 | We addressed the question, how antigen dose shapes the diversity of CD4+ autoreactive T cells specific for glutamate decarboxylase 65 (GAD65) in a healthy HLA-DR*0404+ individual, with a persistent GAD65-specific T-cell response. |
| 2588 | 20370569 | CD4+T cells from this subject were stimulated with decreasing concentrations of the GAD65 555-567 (557I) peptide, and T-cell clones were derived from the tetramer-binding cell population. |
| 2589 | 20370569 | High IL-13 and IL-10 production by GAD65-reactive T cells suggests a more anti-inflammatory profile of this healthy individual underlying protection from T1D. |
| 2590 | 20370569 | A low antigen dose selectively promotes expansion of high-avidity autoreactive T cells with distinct phenotypic characteristics: a study of human autoreactive CD4+T cells specific for GAD65. |
| 2591 | 20370569 | We addressed the question, how antigen dose shapes the diversity of CD4+ autoreactive T cells specific for glutamate decarboxylase 65 (GAD65) in a healthy HLA-DR*0404+ individual, with a persistent GAD65-specific T-cell response. |
| 2592 | 20370569 | CD4+T cells from this subject were stimulated with decreasing concentrations of the GAD65 555-567 (557I) peptide, and T-cell clones were derived from the tetramer-binding cell population. |
| 2593 | 20370569 | High IL-13 and IL-10 production by GAD65-reactive T cells suggests a more anti-inflammatory profile of this healthy individual underlying protection from T1D. |
| 2594 | 20370569 | A low antigen dose selectively promotes expansion of high-avidity autoreactive T cells with distinct phenotypic characteristics: a study of human autoreactive CD4+T cells specific for GAD65. |
| 2595 | 20370569 | We addressed the question, how antigen dose shapes the diversity of CD4+ autoreactive T cells specific for glutamate decarboxylase 65 (GAD65) in a healthy HLA-DR*0404+ individual, with a persistent GAD65-specific T-cell response. |
| 2596 | 20370569 | CD4+T cells from this subject were stimulated with decreasing concentrations of the GAD65 555-567 (557I) peptide, and T-cell clones were derived from the tetramer-binding cell population. |
| 2597 | 20370569 | High IL-13 and IL-10 production by GAD65-reactive T cells suggests a more anti-inflammatory profile of this healthy individual underlying protection from T1D. |
| 2598 | 20406664 | Increased anti-GAD65 IgG1, serum IgA and unchanged IgG2a antibodies titers; together with an increase of IL-4, IL-10 production and a decrease of IFN-gamma production suggested possible activation of GAD65-specific Th2 immune responses. |
| 2599 | 20445565 | The association between the PTPN22 1858C>T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies. |
| 2600 | 20503259 | Characterization of CD4+ T cells specific for glutamic acid decarboxylase (GAD65) and proinsulin in a patient with stiff-person syndrome but without type 1 diabetes. |
| 2601 | 20540111 | Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4(+) T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65(217-230)-specific CD4(+) T cells) using a soluble I-A(αβ) (g7)/GAD65(217-230)/Fcγ2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. |
| 2602 | 20540111 | Activated GAD65(217-230)-specific T cells and a fraction of the diabetogenic (B(9-23)-specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. |
| 2603 | 20540111 | Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4(+) T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65(217-230)-specific CD4(+) T cells) using a soluble I-A(αβ) (g7)/GAD65(217-230)/Fcγ2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. |
| 2604 | 20540111 | Activated GAD65(217-230)-specific T cells and a fraction of the diabetogenic (B(9-23)-specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. |
| 2605 | 20580618 | Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. |
| 2606 | 20969926 | Administration of dendritic cells dual expressing DcR3 and GAD65 mediates the suppression of T cells and induces long-term acceptance of pancreatic-islet transplantation. |
| 2607 | 20969926 | In this study, dendritic cells (DCs) were transfected with the recombinant adenovirus, dual expressing DcR3 and GAD65 in vitro, and NOD mice were administrated with the genetically modified DCs in vivo after islet transplantation. |
| 2608 | 20969926 | The findings suggest that the adoptive transfer of genetically modified DCs dual expressing DcR3 and GAD65 represent a future therapeutic potential in T1D and pancreatic-islet transplantation. |
| 2609 | 20969926 | Administration of dendritic cells dual expressing DcR3 and GAD65 mediates the suppression of T cells and induces long-term acceptance of pancreatic-islet transplantation. |
| 2610 | 20969926 | In this study, dendritic cells (DCs) were transfected with the recombinant adenovirus, dual expressing DcR3 and GAD65 in vitro, and NOD mice were administrated with the genetically modified DCs in vivo after islet transplantation. |
| 2611 | 20969926 | The findings suggest that the adoptive transfer of genetically modified DCs dual expressing DcR3 and GAD65 represent a future therapeutic potential in T1D and pancreatic-islet transplantation. |
| 2612 | 20969926 | Administration of dendritic cells dual expressing DcR3 and GAD65 mediates the suppression of T cells and induces long-term acceptance of pancreatic-islet transplantation. |
| 2613 | 20969926 | In this study, dendritic cells (DCs) were transfected with the recombinant adenovirus, dual expressing DcR3 and GAD65 in vitro, and NOD mice were administrated with the genetically modified DCs in vivo after islet transplantation. |
| 2614 | 20969926 | The findings suggest that the adoptive transfer of genetically modified DCs dual expressing DcR3 and GAD65 represent a future therapeutic potential in T1D and pancreatic-islet transplantation. |
| 2615 | 21050716 | To this end, we determined the feasibility of cloning and expanding human CD4(+) Treg specific for the type 1 diabetes autoantigens, GAD65 and proinsulin. |
| 2616 | 21050716 | Blood CD4(+) cells stimulated to divide in response to GAD65 (in three healthy individuals) or proinsulin (in one type 1 diabetic) were flow sorted into single cells and cultured on feeder cells in the presence of anti-CD3 monoclonal antibody, IL-2 and IL-4. |
| 2617 | 21050716 | Treg clones were not distinguished by markers of conventional CD4(+)CD25(+) Treg and suppressed independently of cell-cell contact but not via known soluble suppressor factors. |
| 2618 | 21263221 | Does immune-tolerance treatment with Alum-formulated GAD65 protect insulin-production in the pancreatic islet β cells? |
| 2619 | 21604002 | Antibodies to GAD65 and IA-2 were determined by radioimmunoassay. |
| 2620 | 21604002 | IA-2 autoantibodies did correlate neither with EV-RNA nor with insulin resistance. |
| 2621 | 21911777 | A longitudinal study of GAD65 and ICA512 autoantibodies during the progression to type 1 diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants. |
| 2622 | 22174945 | A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). |
| 2623 | 22174945 | Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). |
| 2624 | 22174945 | Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. |
| 2625 | 22174945 | Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. |
| 2626 | 22174945 | In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity. |
| 2627 | 22174945 | A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). |
| 2628 | 22174945 | Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). |
| 2629 | 22174945 | Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. |
| 2630 | 22174945 | Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. |
| 2631 | 22174945 | In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity. |
| 2632 | 22174945 | A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). |
| 2633 | 22174945 | Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). |
| 2634 | 22174945 | Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. |
| 2635 | 22174945 | Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. |
| 2636 | 22174945 | In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity. |
| 2637 | 22174945 | A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). |
| 2638 | 22174945 | Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). |
| 2639 | 22174945 | Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. |
| 2640 | 22174945 | Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. |
| 2641 | 22174945 | In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity. |
| 2642 | 22385239 | In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1β, tumour necrosis factor (TNF)-α, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). |
| 2643 | 22385239 | Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0·80; P = 0·000), IL-8 and TNF-α (r = 0·60; P = 0·000); IL-8 and IL-12 (r = 0·57; P = 0·001) and TNF-α and IL-12 (r = 0·93; P = 0·000). |
| 2644 | 22385239 | Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = -0·45; P = 0·011) and CCL2 (r = -0·65; P = 0·000), while IA-2A showed a negative correlation with IL-10 (r = -0·38; P = 0·027). |
| 2645 | 22385239 | Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. |
| 2646 | 22519592 | We observed a decreased expression of bad, bax and fasL pro-apoptotic genes and an increased expression of a1, bcl-x(L) and cIAP-2 anti-apoptotic genes in patients' peripheral blood mononuclear cells (PBMCs) compared to controls. |
| 2647 | 22519592 | After HDI-AHSCT, we found an up-regulation of fas and fasL and a down-regulation of anti-apoptotic bcl-x(L) genes expression in post-HDI-AHSCT periods compared to pre-transplantation. |
| 2648 | 22519592 | Additionally, the levels of bad, bax, bok, fasL, bcl-x(L) and cIAP-1 genes expression were found similar to controls 2 years after HDI-AHSCT. |
| 2649 | 22519592 | Furthermore, over-expression of pro-apoptotic noxa at 540 days post-HDI-AHSCT correlated positively with insulin-free patients and conversely with glutamic acid decarboxylase autoantibodies (GAD65) autoantibody levels. |
| 2650 | 22567309 | The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. |
| 2651 | 22567309 | In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. |
| 2652 | 22893260 | FP eluates were tested using both single and combined assay for antibodies to glutamic acid decarboxylase (GADA) and/or to the protein tyrosine phosphatase like IA-2 (IA-2A), and a single assay for antibodies to insulin (IAA). |
| 2653 | 22893260 | The GADA and IA-2A were measured by radio-binding assays, which utilize 35S-labeled GAD65 and IA-2. |
| 2654 | 22908193 | In this context, we evaluate the biochemical nature and immunogenicity of the major autoantigens in T1D including (pro)insulin, GAD65, ZnT8, IA2, and ICA69. |
| 2655 | 23028856 | Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. |
| 2656 | 23028856 | A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). |
| 2657 | 23226634 | Several experimental and clinical trials of applying GAD65, Hsp60, peptide-MHC, pepetide-277 immunization, anti-CD3 infusion, and interleukins to modulate immune response in T1DM were done. |
| 2658 | 23235561 | We compared four different HSV1-based vectors engineered to produce one of two opioid receptor agonists (enkephalin or endomorphin), or one of two isoforms of glutamic acid decarboxylase (GAD65 or GAD67), alone and in combination, in the streptozotocin-induced diabetic rat and mouse models. |
| 2659 | 23296174 | Autoantibodies against insulin, GAD65, IA-2 or the ZnT8 transporter mark islet autoimmunity. |
| 2660 | 23349478 | We found naïve proinsulin- and GAD65-responsive T cells in cord blood (CB) of healthy newborns, with highest responses observed in children with type 1 diabetes-susceptible HLA-DRB1/DQB1 genotypes. |
| 2661 | 23480181 | The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort. |
| 2662 | 23480181 | Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. |
| 2663 | 23480181 | We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). |
| 2664 | 23480181 | We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. |
| 2665 | 23480181 | The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. |
| 2666 | 23480181 | The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. |
| 2667 | 23480181 | In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. |
| 2668 | 23480181 | The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies. |
| 2669 | 23480181 | The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort. |
| 2670 | 23480181 | Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. |
| 2671 | 23480181 | We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). |
| 2672 | 23480181 | We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. |
| 2673 | 23480181 | The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. |
| 2674 | 23480181 | The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. |
| 2675 | 23480181 | In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. |
| 2676 | 23480181 | The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies. |
| 2677 | 23480181 | The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort. |
| 2678 | 23480181 | Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. |
| 2679 | 23480181 | We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). |
| 2680 | 23480181 | We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. |
| 2681 | 23480181 | The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. |
| 2682 | 23480181 | The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. |
| 2683 | 23480181 | In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. |
| 2684 | 23480181 | The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies. |
| 2685 | 23600827 | Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. |
| 2686 | 23600827 | In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. |
| 2687 | 23600827 | Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. |
| 2688 | 23600827 | GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. |
| 2689 | 23600827 | Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). |
| 2690 | 23600827 | In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment. |
| 2691 | 23600827 | Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. |
| 2692 | 23600827 | In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. |
| 2693 | 23600827 | Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. |
| 2694 | 23600827 | GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. |
| 2695 | 23600827 | Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). |
| 2696 | 23600827 | In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment. |
| 2697 | 23600827 | Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. |
| 2698 | 23600827 | In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. |
| 2699 | 23600827 | Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. |
| 2700 | 23600827 | GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. |
| 2701 | 23600827 | Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). |
| 2702 | 23600827 | In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment. |
| 2703 | 23600827 | Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. |
| 2704 | 23600827 | In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. |
| 2705 | 23600827 | Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. |
| 2706 | 23600827 | GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. |
| 2707 | 23600827 | Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). |
| 2708 | 23600827 | In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment. |
| 2709 | 23770292 | Glutamic acid decarboxylase of 65 kDa (GAD65) is a major autoantigen in type 1 diabetes (T1D) and GAD-specific autoimmunity is a common feature of T1D in humans but also in mouse models of the disease. |
| 2710 | 23770292 | Consistent with the latest clinical trials, mice treated with GAD-alum were not protected from diabetes, although GAD-alum induced a GAD-specific Th2-deviated immune response in transgenic rat insulin promoter-glycoprotein (RIP-GP) mice. |
| 2711 | 23841104 | PBMCs from these individuals were stimulated with a cocktail of diabetes-associated autoantigens (proinsulin, IA-2, and GAD65-derived peptides). |
| 2712 | 23900975 | Currently, four major molecular targets ([pro]insulin, GAD65, IA-2, and ZnT8) have been confirmed, with approximately 94% of all subjects with a clinical diagnosis of type 1 diabetes expressing autoantibodies to at least one of these molecules at clinical onset. |
| 2713 | 23928796 | Circulating primary CD4(+) or CD8(+) T cells were quantified with 5-color flow cytometry. |
| 2714 | 23928796 | Serum IL-22 and IL-17 levels were examined by ELISA. |
| 2715 | 23928796 | Serum autoantibodies were measured by radio-binding assays, using (35)S-labeled glutamic acid decarboxylase-65 (GAD65), protein tyrosine phosphatase-2 (IA-2), and zinc transporter 8 (ZnT8). |
| 2716 | 23928796 | However, we did not find any correlation between IL-17 and IL-22 in sera. |
| 2717 | 23974918 | The assay was validated with serum samples from 227 newly diagnosed diabetic children; 68 prediabetic children who were prospectively followed to T1D; 130 nondiabetic children with confirmed islet autoantibodies to insulin, GAD65, IA-2, and/or ZnT8 longitudinally followed for 12 ± 3.7 years; and 181 age-matched, healthy, antibody-negative children. |