Ignet

Gene Information

Gene symbol: SMCR

Gene name: Smith-Magenis syndrome chromosome region

HGNC ID: 11113

Related Genes

#	Gene Symbol	Number of hits
1	CD4	1 hits
2	GAD1	1 hits
3	GAD2	1 hits
4	IDDM2	1 hits
5	INS	1 hits
6	KLK3	1 hits

Related Sentences

#	PMID	Sentence
1	1722364	Autoimmunity to glutamic acid decarboxylase (GAD) in Stiff-Man syndrome and insulin-dependent diabetes mellitus.
2	1722364	It is also a putative signal molecule in the pancreas, where it is produced by beta cells (insulin-secreting cells)--the autoimmune target in insulin-dependent diabetes mellitus (IDDM).
3	1722364	Autoantibodies to the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) have been found in SMS and in IDDM.
4	1722364	This review summarizes evidence suggesting that SMS may be an autoimmune disease and discusses the possible significance of the autoimmune response to GAD in SMS and IDDM.
5	1722364	Autoimmunity to glutamic acid decarboxylase (GAD) in Stiff-Man syndrome and insulin-dependent diabetes mellitus.
6	1722364	It is also a putative signal molecule in the pancreas, where it is produced by beta cells (insulin-secreting cells)--the autoimmune target in insulin-dependent diabetes mellitus (IDDM).
7	1722364	Autoantibodies to the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) have been found in SMS and in IDDM.
8	1722364	This review summarizes evidence suggesting that SMS may be an autoimmune disease and discusses the possible significance of the autoimmune response to GAD in SMS and IDDM.
9	7505244	GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes.
10	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).
11	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.
12	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.
13	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.
14	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.
15	7505244	GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes.
16	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).
17	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.
18	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.
19	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.
20	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.
21	7505244	GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes.
22	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).
23	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.
24	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.
25	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.
26	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.
27	7505244	GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes.
28	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).
29	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.
30	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.
31	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.
32	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.
33	7505244	GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes.
34	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).
35	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.
36	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.
37	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.
38	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.
39	7511084	The frequency of antibodies to GAD (anti-GAD) in insulin-dependent diabetes mellitus (IDDM) varies greatly according to the type of assay employed.
40	7511084	Sera from 38 patients with IDDM, including 1 patient with both stiff-man syndrome (SMS) and IDDM, were studied for anti-GAD by radioimmunoprecipitation (RIP), Western blotting, and dot-blotting.
41	7511084	There was a good correlation between potency of the RIP reaction at the screening dilution of 1:2 and the endpoint dilution in the assay which ranged from 1:2 to 1:30,000 for IDDM sera, and 1:300,000 for the SMS serum.
42	7511084	Thus, using a dot-blotting assay in which reactivity to untreated "native" GAD was compared with reactivity to GAD after denaturation by reduction with 2-mercaptoethanol and boiling, 20 of the 38 IDDM sera reacted unequivocally with the native GAD compared with only 2 that reacted with denatured GAD after reduction and boiling.
43	7511084	The sera were tested for their capacity to inhibit the catalytic activity of GAD, but only the high-titer serum from the patient with SMS did so.
44	7511084	Our study further validates the RIP assay for anti-GAD and establishes that anti-GAD exists in IDDM over a wide range of titers that correlate with other assay characteristics, and also indicates that the conformational autoantibody epitope on GAD is susceptible to alteration under denaturing conditions.
45	7511084	The frequency of antibodies to GAD (anti-GAD) in insulin-dependent diabetes mellitus (IDDM) varies greatly according to the type of assay employed.
46	7511084	Sera from 38 patients with IDDM, including 1 patient with both stiff-man syndrome (SMS) and IDDM, were studied for anti-GAD by radioimmunoprecipitation (RIP), Western blotting, and dot-blotting.
47	7511084	There was a good correlation between potency of the RIP reaction at the screening dilution of 1:2 and the endpoint dilution in the assay which ranged from 1:2 to 1:30,000 for IDDM sera, and 1:300,000 for the SMS serum.
48	7511084	Thus, using a dot-blotting assay in which reactivity to untreated "native" GAD was compared with reactivity to GAD after denaturation by reduction with 2-mercaptoethanol and boiling, 20 of the 38 IDDM sera reacted unequivocally with the native GAD compared with only 2 that reacted with denatured GAD after reduction and boiling.
49	7511084	The sera were tested for their capacity to inhibit the catalytic activity of GAD, but only the high-titer serum from the patient with SMS did so.
50	7511084	Our study further validates the RIP assay for anti-GAD and establishes that anti-GAD exists in IDDM over a wide range of titers that correlate with other assay characteristics, and also indicates that the conformational autoantibody epitope on GAD is susceptible to alteration under denaturing conditions.
51	7511084	The frequency of antibodies to GAD (anti-GAD) in insulin-dependent diabetes mellitus (IDDM) varies greatly according to the type of assay employed.
52	7511084	Sera from 38 patients with IDDM, including 1 patient with both stiff-man syndrome (SMS) and IDDM, were studied for anti-GAD by radioimmunoprecipitation (RIP), Western blotting, and dot-blotting.
53	7511084	There was a good correlation between potency of the RIP reaction at the screening dilution of 1:2 and the endpoint dilution in the assay which ranged from 1:2 to 1:30,000 for IDDM sera, and 1:300,000 for the SMS serum.
54	7511084	Thus, using a dot-blotting assay in which reactivity to untreated "native" GAD was compared with reactivity to GAD after denaturation by reduction with 2-mercaptoethanol and boiling, 20 of the 38 IDDM sera reacted unequivocally with the native GAD compared with only 2 that reacted with denatured GAD after reduction and boiling.
55	7511084	The sera were tested for their capacity to inhibit the catalytic activity of GAD, but only the high-titer serum from the patient with SMS did so.
56	7511084	Our study further validates the RIP assay for anti-GAD and establishes that anti-GAD exists in IDDM over a wide range of titers that correlate with other assay characteristics, and also indicates that the conformational autoantibody epitope on GAD is susceptible to alteration under denaturing conditions.
57	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.
58	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.
59	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
60	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
61	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
62	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.
63	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.
64	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.
65	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.
66	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.
67	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.
68	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
69	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
70	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
71	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.
72	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.
73	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.
74	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.
75	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.
76	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.
77	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
78	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
79	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
80	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.
81	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.
82	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.
83	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.
84	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.
85	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.
86	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
87	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
88	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
89	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.
90	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.
91	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.
92	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.
93	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.
94	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.
95	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
96	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
97	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
98	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.
99	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.
100	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.
101	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.
102	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.
103	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.
104	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
105	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
106	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
107	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.
108	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.
109	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.
110	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.
111	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.
112	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.
113	7519242	Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM.
114	7519242	All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients.
115	7519242	Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots.
116	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.
117	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.
118	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.
119	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.
120	7926297	Apart from islet cell antibodies (ICAs), antibodies to glutamate decarboxylase (GAD), insulin autoantibodies (IAAs), and a novel islet antigen (37k antigen) are potential markers for insulin-dependent diabetes mellitus (IDDM).
121	7926297	GAD is also an antigen in stiff-man syndrome (SMS), and both SMS and IDDM are associated with ICAs and autoimmunity to other endocrine organs.
122	7926297	Antibodies to GAD were detected in > or = 90% of both diabetic and nondiabetic patients with ICAs and other endocrine autoimmunity, in 59% of ICA-positive IDDM patients without endocrine autoimmunity, in all patients with SMS, but in only 1-3% of healthy (nondiabetic) and autoimmune disease control subjects.
123	7926297	GAD antibody levels were increased in ICA-positive IDDM patients with polyendocrine autoimmunity compared with those without.
124	7926297	Thus, certain factors enhance antibody responses to GAD in polyendocrine autoimmunity, but this does not necessarily lead to development of IDDM or SMS.
125	7926297	Apart from islet cell antibodies (ICAs), antibodies to glutamate decarboxylase (GAD), insulin autoantibodies (IAAs), and a novel islet antigen (37k antigen) are potential markers for insulin-dependent diabetes mellitus (IDDM).
126	7926297	GAD is also an antigen in stiff-man syndrome (SMS), and both SMS and IDDM are associated with ICAs and autoimmunity to other endocrine organs.
127	7926297	Antibodies to GAD were detected in > or = 90% of both diabetic and nondiabetic patients with ICAs and other endocrine autoimmunity, in 59% of ICA-positive IDDM patients without endocrine autoimmunity, in all patients with SMS, but in only 1-3% of healthy (nondiabetic) and autoimmune disease control subjects.
128	7926297	GAD antibody levels were increased in ICA-positive IDDM patients with polyendocrine autoimmunity compared with those without.
129	7926297	Thus, certain factors enhance antibody responses to GAD in polyendocrine autoimmunity, but this does not necessarily lead to development of IDDM or SMS.
130	7926297	Apart from islet cell antibodies (ICAs), antibodies to glutamate decarboxylase (GAD), insulin autoantibodies (IAAs), and a novel islet antigen (37k antigen) are potential markers for insulin-dependent diabetes mellitus (IDDM).
131	7926297	GAD is also an antigen in stiff-man syndrome (SMS), and both SMS and IDDM are associated with ICAs and autoimmunity to other endocrine organs.
132	7926297	Antibodies to GAD were detected in > or = 90% of both diabetic and nondiabetic patients with ICAs and other endocrine autoimmunity, in 59% of ICA-positive IDDM patients without endocrine autoimmunity, in all patients with SMS, but in only 1-3% of healthy (nondiabetic) and autoimmune disease control subjects.
133	7926297	GAD antibody levels were increased in ICA-positive IDDM patients with polyendocrine autoimmunity compared with those without.
134	7926297	Thus, certain factors enhance antibody responses to GAD in polyendocrine autoimmunity, but this does not necessarily lead to development of IDDM or SMS.
135	8039593	Glutamic acid decarboxylase antibodies (GADAbs) are being increasingly used in clinical and research programs for the prediction and classification of insulin-dependent diabetes mellitus (IDDM).
136	8039593	The 16 lyophilized coded samples consisted of sera from healthy control subjects (n = 2), IDDM patients (n = 3), a patient with polyendocrine autoimmunity (n = 1), and duplicate dilutions of plasmapheresis serum from a patient with stiff-man syndrome (SMS).
137	8039593	Thirteen (38%) assays could reproducibly distinguish dilutions of SMS serum and detect GADAbs in all IDDM and polyendocrine autoimmunity sera tested.
138	8039593	Several assays, in particular those measuring GAD enzymatic activity immunoprecipitated in fluid phase from rat brain homogenate, showed a prozone-like phenomenon in the SMS dilution curve.
139	8039593	Glutamic acid decarboxylase antibodies (GADAbs) are being increasingly used in clinical and research programs for the prediction and classification of insulin-dependent diabetes mellitus (IDDM).
140	8039593	The 16 lyophilized coded samples consisted of sera from healthy control subjects (n = 2), IDDM patients (n = 3), a patient with polyendocrine autoimmunity (n = 1), and duplicate dilutions of plasmapheresis serum from a patient with stiff-man syndrome (SMS).
141	8039593	Thirteen (38%) assays could reproducibly distinguish dilutions of SMS serum and detect GADAbs in all IDDM and polyendocrine autoimmunity sera tested.
142	8039593	Several assays, in particular those measuring GAD enzymatic activity immunoprecipitated in fluid phase from rat brain homogenate, showed a prozone-like phenomenon in the SMS dilution curve.
143	8039593	Glutamic acid decarboxylase antibodies (GADAbs) are being increasingly used in clinical and research programs for the prediction and classification of insulin-dependent diabetes mellitus (IDDM).
144	8039593	The 16 lyophilized coded samples consisted of sera from healthy control subjects (n = 2), IDDM patients (n = 3), a patient with polyendocrine autoimmunity (n = 1), and duplicate dilutions of plasmapheresis serum from a patient with stiff-man syndrome (SMS).
145	8039593	Thirteen (38%) assays could reproducibly distinguish dilutions of SMS serum and detect GADAbs in all IDDM and polyendocrine autoimmunity sera tested.
146	8039593	Several assays, in particular those measuring GAD enzymatic activity immunoprecipitated in fluid phase from rat brain homogenate, showed a prozone-like phenomenon in the SMS dilution curve.
147	8245784	It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus.
148	8245784	The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes.
149	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.
150	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).
151	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.
152	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.
153	8245784	It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus.
154	8245784	The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes.
155	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.
156	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).
157	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.
158	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.
159	8245784	It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus.
160	8245784	The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes.
161	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.
162	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).
163	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.
164	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.
165	8245784	It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus.
166	8245784	The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes.
167	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.
168	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).
169	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.
170	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.
171	8263140	Patients with SMS often have other autoimmune diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM).
172	8263140	Similar to SMS, the majority of patients with IDDM have autoantibodies against glutamic acid decarboxylase at or before diabetes onset, although usually at a lower titer and with a different reaction pattern than patients with SMS.
173	8263140	Patients with SMS carried the IDDM-protective DQB10602 allele and other sequence-related DQB106 alleles with the same frequency observed in controls.
174	8263140	Patients with SMS often have other autoimmune diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM).
175	8263140	Similar to SMS, the majority of patients with IDDM have autoantibodies against glutamic acid decarboxylase at or before diabetes onset, although usually at a lower titer and with a different reaction pattern than patients with SMS.
176	8263140	Patients with SMS carried the IDDM-protective DQB10602 allele and other sequence-related DQB106 alleles with the same frequency observed in controls.
177	8263140	Patients with SMS often have other autoimmune diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM).
178	8263140	Similar to SMS, the majority of patients with IDDM have autoantibodies against glutamic acid decarboxylase at or before diabetes onset, although usually at a lower titer and with a different reaction pattern than patients with SMS.
179	8263140	Patients with SMS carried the IDDM-protective DQB10602 allele and other sequence-related DQB106 alleles with the same frequency observed in controls.
180	8543838	Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS).
181	8543838	Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM.
182	8543838	The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563.
183	8543838	These types of GAD Abs are not found in IDDM sera.
184	8543838	All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65.
185	8543838	In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein.
186	8543838	These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM.
187	8543838	Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS).
188	8543838	Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM.
189	8543838	The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563.
190	8543838	These types of GAD Abs are not found in IDDM sera.
191	8543838	All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65.
192	8543838	In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein.
193	8543838	These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM.
194	8543838	Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS).
195	8543838	Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM.
196	8543838	The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563.
197	8543838	These types of GAD Abs are not found in IDDM sera.
198	8543838	All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65.
199	8543838	In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein.
200	8543838	These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM.
201	8543838	Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS).
202	8543838	Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM.
203	8543838	The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563.
204	8543838	These types of GAD Abs are not found in IDDM sera.
205	8543838	All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65.
206	8543838	In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein.
207	8543838	These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM.
208	8543838	Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS).
209	8543838	Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM.
210	8543838	The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563.
211	8543838	These types of GAD Abs are not found in IDDM sera.
212	8543838	All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65.
213	8543838	In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein.
214	8543838	These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM.
215	8743289	Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS).
216	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.
217	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.
218	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.
219	8743289	Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS).
220	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.
221	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.
222	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.
223	8823384	The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial.
224	8823384	GAD, in fact, is also one of the major target antigen of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS.
225	8823384	To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned.
226	8823384	Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM.
227	8823384	GAD, ICA 105) does not rule out SMS.
228	8823384	The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial.
229	8823384	GAD, in fact, is also one of the major target antigen of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS.
230	8823384	To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned.
231	8823384	Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM.
232	8823384	GAD, ICA 105) does not rule out SMS.
233	8823384	The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial.
234	8823384	GAD, in fact, is also one of the major target antigen of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS.
235	8823384	To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned.
236	8823384	Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM.
237	8823384	GAD, ICA 105) does not rule out SMS.
238	8823384	The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial.
239	8823384	GAD, in fact, is also one of the major target antigen of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS.
240	8823384	To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned.
241	8823384	Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM.
242	8823384	GAD, ICA 105) does not rule out SMS.
243	8823384	The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial.
244	8823384	GAD, in fact, is also one of the major target antigen of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS.
245	8823384	To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned.
246	8823384	Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM.
247	8823384	GAD, ICA 105) does not rule out SMS.
248	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).
249	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).
250	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.
251	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).
252	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).
253	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.
254	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).
255	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).
256	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.
257	9266148	Besides an insulin-dependent diabetes mellitus (IDDM) she had developed the clinical symptoms of stiff-man-syndrome (SMS) and harbored autoantibodies against glutamate-decarboxylase (GAD) in blood and liquor.
258	9266148	We suggest that this case including GAD autoantibodies, dramatic loss of GAD-expressing pancreatic cells, and loss or atrophy of GABA secretory neurons, supports the hypothesis that SMS may be an autoimmune disease directed against GABA-ergic cells.
259	9266148	Besides an insulin-dependent diabetes mellitus (IDDM) she had developed the clinical symptoms of stiff-man-syndrome (SMS) and harbored autoantibodies against glutamate-decarboxylase (GAD) in blood and liquor.
260	9266148	We suggest that this case including GAD autoantibodies, dramatic loss of GAD-expressing pancreatic cells, and loss or atrophy of GABA secretory neurons, supports the hypothesis that SMS may be an autoimmune disease directed against GABA-ergic cells.
261	9567281	Frequently, SMS remains undiagnosed for prolonged periods or the patients are diagnosed of a primary psychiatric disorder. 60% of the SMS patients harbor GAD-autoantibodies (GAD-Ab).
262	9567281	The GAD-Ab titers were compared with those of 49 patients with insulin-dependent diabetes mellitus (IDDM), 322 with other neurological disorders, 14 non-IDDM first-degree relatives of IDDM patients with antibodies anti-islet cells and 91 normal subjects.
263	9708541	Autoantibodies to the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), present in about 60% of SMS patients, have suggested an autoimmune pathogenesis of SMS.
264	9708541	By using serum or cerebrospinal fluid from 25 SMS patients, we assessed the effect of GAD autoantibodies (GAD-A) on GAD enzymatic activity in vitro; 83% of GAD-A-positive SMS sera reduced GABA production in crude rat cerebellar extracts, whereas GAD-A- sera from SMS patients or healthy blood donors did not alter the enzyme activity.
265	9708541	Human monoclonal GAD65-A and IgG purified from serum of GAD-A-positive patients with insulin-dependent diabetes or autoimmune polyendocrine syndrome did not affect GAD activity, suggesting that a specific epitope recognition of GAD-A mediates inhibition of GAD.
266	9708541	The disease-specific detection of GAD-inhibitory antibodies is compatible with their functional involvement in the etiopathology of SMS; the relevance of such antibodies in vivo, however, remains to be determined.
267	9708541	Autoantibodies to the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), present in about 60% of SMS patients, have suggested an autoimmune pathogenesis of SMS.
268	9708541	By using serum or cerebrospinal fluid from 25 SMS patients, we assessed the effect of GAD autoantibodies (GAD-A) on GAD enzymatic activity in vitro; 83% of GAD-A-positive SMS sera reduced GABA production in crude rat cerebellar extracts, whereas GAD-A- sera from SMS patients or healthy blood donors did not alter the enzyme activity.
269	9708541	Human monoclonal GAD65-A and IgG purified from serum of GAD-A-positive patients with insulin-dependent diabetes or autoimmune polyendocrine syndrome did not affect GAD activity, suggesting that a specific epitope recognition of GAD-A mediates inhibition of GAD.
270	9708541	The disease-specific detection of GAD-inhibitory antibodies is compatible with their functional involvement in the etiopathology of SMS; the relevance of such antibodies in vivo, however, remains to be determined.
271	9708541	Autoantibodies to the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), present in about 60% of SMS patients, have suggested an autoimmune pathogenesis of SMS.
272	9708541	By using serum or cerebrospinal fluid from 25 SMS patients, we assessed the effect of GAD autoantibodies (GAD-A) on GAD enzymatic activity in vitro; 83% of GAD-A-positive SMS sera reduced GABA production in crude rat cerebellar extracts, whereas GAD-A- sera from SMS patients or healthy blood donors did not alter the enzyme activity.
273	9708541	Human monoclonal GAD65-A and IgG purified from serum of GAD-A-positive patients with insulin-dependent diabetes or autoimmune polyendocrine syndrome did not affect GAD activity, suggesting that a specific epitope recognition of GAD-A mediates inhibition of GAD.
274	9708541	The disease-specific detection of GAD-inhibitory antibodies is compatible with their functional involvement in the etiopathology of SMS; the relevance of such antibodies in vivo, however, remains to be determined.
275	9771977	Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of the autoimmune-mediated beta-cell destruction in insulin-dependent (Type I) diabetes.
276	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).
277	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.
278	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.
279	9771977	Autoantibodies to glutamic acid decarboxylase (GAD) are an important marker of the autoimmune-mediated beta-cell destruction in insulin-dependent (Type I) diabetes.
280	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).
281	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.
282	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.
283	9829349	In summary, we describe the first patient with type 1 diabetes, SMS, and severe insulin resistance.
284	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.
285	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.
286	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.
287	10330300	These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0).
288	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.
289	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.
290	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.
291	10330300	These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0).
292	11703367	Thus, oxidatively modified aggregates of GAD react with serum antibodies of type 1 diabetes patients and some SMS patients: this is consistent with oxidative modifications of autoantigens being relevant to the pathogenesis of type 1 diabetes.
293	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.
294	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.
295	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.
296	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.
297	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.
298	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.
299	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.
300	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.
301	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.