Gene name: protein tyrosine phosphatase-like (proline instead of catalytic arginine), member A
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PMID |
Sentence |
1 |
7594559
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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.
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2 |
7594559
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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).
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3 |
7594559
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Recently, autoantibodies against ICA512, which has identity with the protein tyrosine phosphatase-like protein IA2, were reported.
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4 |
7594559
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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.
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5 |
7594559
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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.
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6 |
7594559
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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).
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7 |
7594559
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Recently, autoantibodies against ICA512, which has identity with the protein tyrosine phosphatase-like protein IA2, were reported.
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8 |
7594559
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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.
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9 |
7657822
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Relationship of the 37,000- and 40,000-M(r) tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512).
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10 |
8805677
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Autoantibodies in insulin-dependent diabetes recognize distinct cytoplasmic domains of the protein tyrosine phosphatase-like IA-2 autoantigen.
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11 |
8805677
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Protein tyrosine phosphatase-like IA-2 is a major autoantigen in insulin-dependent diabetes.
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12 |
8805677
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To characterize autoantibody binding to IA-2 and determine whether humoral autoimmunity extends to other tyrosine phosphatases, we analyzed serum reactivity in 100 patients with insulin-dependent diabetes against different in vitro translated portions of the IA-2 protein as well as the tyrosine phosphatase domains of HPTPbeta and HPTPdelta.
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13 |
8805677
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No reactivity against the IA-2 ectodomain or the tyrosine phosphatase domains of HPTPbeta and HPTPdelta was found.
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14 |
8805677
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These data suggest that the cytoplasmic region, in particular the tyrosine phosphatase-like domain, is the major target of IA-2 Abs in insulin-dependent diabetes, and that autoantibody reactivity is specific for IA-2 or IA-2-like molecules.
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15 |
8805677
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Autoantibodies in insulin-dependent diabetes recognize distinct cytoplasmic domains of the protein tyrosine phosphatase-like IA-2 autoantigen.
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16 |
8805677
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Protein tyrosine phosphatase-like IA-2 is a major autoantigen in insulin-dependent diabetes.
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17 |
8805677
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To characterize autoantibody binding to IA-2 and determine whether humoral autoimmunity extends to other tyrosine phosphatases, we analyzed serum reactivity in 100 patients with insulin-dependent diabetes against different in vitro translated portions of the IA-2 protein as well as the tyrosine phosphatase domains of HPTPbeta and HPTPdelta.
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18 |
8805677
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No reactivity against the IA-2 ectodomain or the tyrosine phosphatase domains of HPTPbeta and HPTPdelta was found.
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19 |
8805677
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These data suggest that the cytoplasmic region, in particular the tyrosine phosphatase-like domain, is the major target of IA-2 Abs in insulin-dependent diabetes, and that autoantibody reactivity is specific for IA-2 or IA-2-like molecules.
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20 |
8897011
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Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM.
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21 |
8897011
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Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM).
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22 |
8897011
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We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients.
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23 |
8897011
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The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes.
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24 |
8897011
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At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation by in vitro-translated 35S-methionine labelled recombinant proteins.
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25 |
9118776
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Protein tyrosine phosphatase-like proteins: link with IDDM.
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26 |
9231650
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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.
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27 |
9231650
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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.
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28 |
9231650
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Newly diagnosed type 1 diabetic patients frequently had antibodies to IA-2 (62%), IA-2ic (67%), GAD65 (77%), and ICAs (85%).
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29 |
9231650
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In summary, IA-2 emerges as a major antigen associated with type 1 diabetes and distinct from GAD65.
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30 |
9439455
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Protein tyrosine phosphatase-like protein IA2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus.
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31 |
9439455
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Islet cell antibodies (ICA), the classical autoimmunity marker for insulin-dependent diabetes mellitus (IDDM), are detected in approximately 85% of children with recently diagnosed diabetes.
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32 |
9439455
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Now, antibodies against the protein tyrosine phosphatase-like protein IA2 (IA2-ab) have been detected in IDDM.
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33 |
9439455
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Protein tyrosine phosphatase-like protein IA2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus.
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34 |
9439455
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Islet cell antibodies (ICA), the classical autoimmunity marker for insulin-dependent diabetes mellitus (IDDM), are detected in approximately 85% of children with recently diagnosed diabetes.
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35 |
9439455
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Now, antibodies against the protein tyrosine phosphatase-like protein IA2 (IA2-ab) have been detected in IDDM.
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36 |
9605631
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IA-2 and IA-2beta: the immune response in IDDM.
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37 |
9605631
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Pancreatic islet cell autoantigens associated with insulin-dependent diabetes mellitus (IDDM) include a recently identified family of protein tyrosine phosphatase-like molecules, notably IA-2 and IA-2beta.
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38 |
9605631
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IA-2 is a 979 amino acid transmembrane protein located on human chromosome 2q35, whereas IA-2beta is 986 amino acids long located on human chromosome 7q36.
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39 |
9605631
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Comparison of human IA-2 and IA-2beta showed 74% identity within the intercellular domains, but only 27% indentify within the extracellular domains.
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40 |
9605631
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Radioimmunoprecipitation with recombinant IA-2 and IA-2beta has been used to measure autoantibodies to these molecules and their intracellular fragments.
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41 |
9605631
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Autoantibodies to IA-2 are detected in the majority (60% to 80%) of newly diagnosed IDDM patients and in less than 2% of controls.
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42 |
9605631
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The major antigenic determinants of both IA-2 and IA-2beta reside within the C-terminus of their intracellular domains.
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43 |
9605631
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In first-degree relatives of IDDM patients, the presence of autoantibodies to IA-2 is predictive of IDDM and in combination with autoantibodies to glutamic acid decarboxylase (GAD) the positive predictive value is in the 50% range.
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44 |
9605631
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The role of IA-2 and IA-2beta in the pathogenesis of IDDM is still unclear.
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45 |
9714834
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Recently, there have been several reports describing the cloning and characterization of the novel family of protein tyrosine phosphatase-like receptor molecules (known as IA-2 and PTP-NP/PTP-IAR/IA-2beta/phogrin), which may act as autoantigens in diabetes.
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46 |
10479394
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To elucidate the associations of expression of autoantibodies to multiple islet antigens with age of onset and mode of diagnosis of diabetes in Japanese patients with type 1 diabetes, autoantibodies against the protein tyrosine phosphatase-like molecules ICA512 (IA-2) and phogrin (IA-2beta) (ICA512/phogrin-A), GAD (GADA), insulin (IAA), and islet cell cytoplasm (ICA) were determined in sera from 73 Japanese patients with type 1 diabetes obtained within 14 days of diagnosis.
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47 |
10479394
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The frequency of ICA512/phogrin-A was significantly higher in patients with an age of onset less than 10 years (83%) than in patients aged >10 years (51%, P<0.01).
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48 |
10479394
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The positivity of ICA512/phogrin-A was less in patients whose diabetes was diagnosed by the urine glucose screening test (21%, P<0.001) than in abrupt onset patients (71%).
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49 |
10479394
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Combined analysis (>/=1 antibody) of GADA, IAA, and ICA512/phogrin-A detected 88% of abrupt onset and 93% of screening-positive patients vs. 70% and 29%, respectively, for ICA (P<0.0005).
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50 |
10479394
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These results indicate that the expression of ICA512/phogrin-A and cytoplasmic ICA is less in patients identified by urinary glucose testing but indicate that with combined autoantibody testing 90% of patients can be identified independent of the mode of diagnosis.
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51 |
10677057
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The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes.
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52 |
11035111
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Human monoclonal antibodies isolated from type I diabetes patients define multiple epitopes in the protein tyrosine phosphatase-like IA-2 antigen.
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53 |
11035111
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Protein tyrosine phosphatase-like IA-2 autoantigen is one of the major targets of humoral autoimmunity in patients with insulin-dependant diabetes mellitus (IDDM).
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54 |
11035111
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In an effort to define the epitopes recognized by autoantibodies against IA-2, we generated five human mAbs (hAbs) from peripheral B lymphocytes isolated from patients most of whom had been recently diagnosed for IDDM.
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55 |
11035111
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Determination and fine mapping of the critical regions for autoantibody binding was performed by RIA using mutant and chimeric constructs of IA-2- and IA-2beta-regions.
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56 |
11035111
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Four of the five IgG autoantibodies recognized distinct epitopes within the protein tyrosine phosphatase (PTP)-like domain of IA-2.
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57 |
11035111
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Two of these hAbs cross-reacted with the related IA-2beta PTP-like domain (IA-2beta aa 741-1033).
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58 |
11035111
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Human monoclonal antibodies isolated from type I diabetes patients define multiple epitopes in the protein tyrosine phosphatase-like IA-2 antigen.
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59 |
11035111
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Protein tyrosine phosphatase-like IA-2 autoantigen is one of the major targets of humoral autoimmunity in patients with insulin-dependant diabetes mellitus (IDDM).
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60 |
11035111
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In an effort to define the epitopes recognized by autoantibodies against IA-2, we generated five human mAbs (hAbs) from peripheral B lymphocytes isolated from patients most of whom had been recently diagnosed for IDDM.
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61 |
11035111
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Determination and fine mapping of the critical regions for autoantibody binding was performed by RIA using mutant and chimeric constructs of IA-2- and IA-2beta-regions.
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62 |
11035111
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Four of the five IgG autoantibodies recognized distinct epitopes within the protein tyrosine phosphatase (PTP)-like domain of IA-2.
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63 |
11035111
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Two of these hAbs cross-reacted with the related IA-2beta PTP-like domain (IA-2beta aa 741-1033).
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64 |
11086294
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IDA-1, a Caenorhabditis elegans homolog of the diabetic autoantigens IA-2 and phogrin, is expressed in peptidergic neurons in the worm.
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11086294
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The closely related mammalian proteins IA-2 and phogrin are protein tyrosine phosphatase-like receptor proteins spanning the membrane of dense core vesicles of neuroendocrine tissues.
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66 |
11086294
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The Caenorhabditis elegans genome has a single copy of an IA-2/phogrin homolog ida-1 III (islet cell diabetic autoantigen), which encodes the ida-1 (B0244.2) gene product as a series of 12 exons over a 10-kb region of chromosome III.
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67 |
11086294
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The PTP catalytic site consensus sequence of IDA-1, like IA-2 and phogrin, diverged and would not be active.
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68 |
11086294
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In situ experiments in rat brain showing the distribution of IA-2 and phogrin suggested a complimentary and overlapping pattern compared with the proprotein convertases PC1 and PC2.
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69 |
11086294
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The results support the hypothesis that C. elegans IDA-1 is the functional homolog of IA-2 and phogrin in mammals.
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70 |
11121550
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Novel fusion proteins in the analysis of diabetes-associated autoantibodies to GAD65 and IA-2.
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71 |
11121550
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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.
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72 |
11121550
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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.
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73 |
11121550
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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.
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74 |
11121550
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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.
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75 |
11121550
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Nine of the samples from patients with type 1 diabetes reacted with GAD65 while being negative for IA-2.
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76 |
11121550
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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.
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77 |
11121550
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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.
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11373323
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Expression of the protein tyrosine phosphatase-like protein IA-2 during pancreatic islet development.
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79 |
11373323
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To investigate the potential involvement of IA-2 in islet differentiation and insulin secretion, we analyzed by immunohistochemistry expression of IA-2 during islet development in fetal rats and during the maturation of insulin secretory responses after birth.
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80 |
11373323
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In the fetus, IA-2 immunoreactivity was detected in primitive islets positive for insulin and glucagon at 12 days' gestation.
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81 |
11373323
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Islet IA-2 expression reappears after birth concomitant with the development of mature insulin secretory responses, consistent with a role for this protein in regulated hormone secretion.
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82 |
11488637
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Expression of protein tyrosine phosphatase-like molecule ICA512/IA-2 induces growth arrest in yeast cells and transfected mammalian cell lines.
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83 |
11488637
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In investigations on apoptosis, expression of ICA512/IA-2 in yeast cells caused loss of plasma membrane asymmetry, but not release of cytochrome c from mitochondria which did occur in a control system after expression of the pro-apoptotic molecule Bax.
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84 |
11600216
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The disease is characterized by loss of tolerance to auto-antigens such as GAD, insulin, and the protein tyrosine phosphatase-like molecule, IA-2.
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85 |
11600216
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We identified T cell epitopes on the intracytoplasmic region of IA-2 by immunizing DQ8/NOD, DQ8/B10, and NOD mice with overlapping 18 mer peptides in CFA.
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86 |
11600216
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We demonstrated MHC class II and CD4 restriction of proliferative responses using appropriate blocking antibodies.
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87 |
12017227
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To evaluate the frequency of autoantibodies to glutamic acid decarboxylase (GAD), protein tyrosine phosphatase-like protein (IA-2), and insulin (IAA) in children with type 2 diabetes mellitus (DM), we studied 37 children and adolescents whose type 2 DM was defined by fasting and 90-min standard liquid meal-stimulated serum C-peptide levels of >0.2 and >0.5 nmol/l (0.7 and 1.5 ng/ml), respectively.
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88 |
12017227
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Eleven out of 37 patients (29.7%) were positive for at least one autoantibody: 8.1% (n = 3) had positive GAD, 8.1% (n = 3) had positive IA-2, and 27% (n = 10) had positive IAA.
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89 |
12017227
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Three of the 10 IAA-positive patients were also positive for GAD or IA-2.
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90 |
12017227
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Therefore, GAD and IA-2 were considered primary autoimmune markers.
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91 |
12017227
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Four out of 37 patients (10.8%) were positive for GAD (n = 3) or IA-2 (n = 3) or both (n = 2).
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92 |
12031972
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Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion.
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93 |
12031972
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Glucose tolerance tests, however, revealed statistically significant elevation of glucose in both male and female IA-2(-/-) mice and depressed insulin release.
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94 |
12031972
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We concluded that IA-2 is involved in glucose-stimulated insulin secretion.
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95 |
12765988
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Detection of autoantibodies to protein tyrosine phosphatase-like protein IA-2 with a novel time-resolved fluorimetric assay.
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96 |
14747289
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Family history of type 1 diabetes and autoantibodies to the islet antigens insulin (IAA), glutamate decarboxylase (GADA), and the protein tyrosine phosphatase-like protein IA-2 (IA-2A) are strong predictors of type 1 diabetes, but the rate of progression to diabetes in multiple islet autoantibody-positive relatives varies widely.
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97 |
14747289
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The highest risks were associated with high-titer IA-2A and IAA, IgG2, IgG3, and/or IgG4 subclass of IA-2A and IAA, and antibodies to the IA-2-related molecule IA-2beta.
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98 |
15240119
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Autoantibodies against IA-2, GAD, and topoisomerase II in type 1 diabetic patients.
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99 |
15240119
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Eighty percent of the IA-2A recognized the carboxyl terminus of the IA-2 protein tyrosine phosphatase-like domain.
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100 |
15826925
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Autoantibodies against islet antigens such as insulin, glutamic acid decarboxylase, and the protein tyrosine phosphatase-like molecule IA-2 are found in most patients with type 1 diabetes and are now established markers for the clinical diagnosis and the preclinical phase of this disease.
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101 |
15829408
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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.
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102 |
15829408
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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.
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103 |
15829408
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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.
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104 |
15829408
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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.
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105 |
16442659
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Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes.
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106 |
16442659
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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.
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107 |
16442659
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The differences remained even when the patients were matched for HLA, insulin and CTLA-4 risk genotypes.
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108 |
16442659
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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.
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109 |
19120305
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These results emphasize the heterogeneity of humoral autoimmunity to protein tyrosine phosphatase-like molecules, but not to GAD, in patients with type 1 diabetes.
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110 |
22893260
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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).
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111 |
22893260
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The GADA and IA-2A were measured by radio-binding assays, which utilize 35S-labeled GAD65 and IA-2.
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