Cloning and expression of IDDM-specific human autoantigens

Rabin, David; Pleasic, S. M.; Palmer-Crocker, Rebecca; Shapiro, J. A.

doi:10.2337/diabetes.41.2.183

Cited by 76 publications

(56 citation statements)

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“…IAA. In the exploratory analysis, the unadjusted frequency of IAA increased with the number of class I alleles of INS VNTR: 15% of III/III patients (95% CI 0 -30), 30% of I/III patients (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), and 40% of I/I patients (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) were positive for IAA. Unadjusted frequencies of IAA were higher in DQ8-positive than in DQ8-negative patients: 27% of patients with no DQ8 haplotypes (95% CI 20 -34), 41% of patients with one DQ8 haplotype (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46), and 42% of patients with two DQ8 haplotypes (26 -57) were positive for IAA.…”

Section: Resultsmentioning

confidence: 99%

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Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

et al. 2002

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Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0 -34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P ‫؍‬ 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P ‫؍‬ 0.03) and with INS VNTR (P ‫؍‬ 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P ‫؍‬ 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P ‫؍‬ 0.04), and all four autoantibody markers (P ‫؍‬ 0.004). The CTLA-4 3 end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development. Diabetes 51: 1346 -1355, 2002

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Section: Resultsmentioning

confidence: 99%

“…Islet antigen-2 or ICA512 autoantibodies. Antibodies to ICA512/IA-2 (ICA512) (12,32) were measured by radiobinding immunoassay (33). The 3Ј portion of the ICA512cDNA (32) corresponding to the cytoplasmic portion of the protein (residues 602-979) was amplified by RT-PCR from human HTB-14 glioblastoma cells (12).…”

Section: Insulin Gene Vntr (Iddm2)mentioning

confidence: 99%

Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

et al. 2002

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“…It is widely recognised, however, that Type I diabetes can develop at any age which complicates classification in the older patient. Type I diabetes in children and young adults is strongly associated with the presence of autoantibodies against the Mr 65 kD isoform of glutamate decarboxylase (GAD65) [2] and IA-2 (ICA512), a tyrosine phosphatase-like transmembrane protein [3,4]. The diagnostic sensitivity of GAD65Ab has been reported to be about 70±80 % and the diagnostic specificity 99 % in such patients [5].…”

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confidence: 99%

Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index

et al. 1999

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The clinical diagnosis of diabetes mellitus is based on specific criteria of blood glucose concentrations [1]. After diagnosis of the disease, clinical criteria are used to classify diabetes into Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. The classification of diabetes is mostly unambiguous in people younger than 20 years of age and in older patients who predominately have Type II diabetes. It is widely recognised, however, that Type I diabetes can develop at any age which complicates classification in the older patient. Type I diabetes in children and young adults is strongly associated with the presence of autoantibodies against the Mr 65 kD isoform of glutamate decarboxylase (GAD65) [2] and IA-2 (ICA512), a tyrosine phosphatase-like transmembrane protein [3,4]. The diagnostic sensitivity of GAD65Ab has been reported to be about 70±80 % and the diagnostic specificity 99 % in such patients [5]. Furthermore, in newly diagnosed Type Diabetologia (1999) Results. We found 23 of 2157 (1.1 %) and 17 of 2152 (0.8 %) subjects exceeded the 99th centile of GAD65 autoantibody index and IA-2 autoantibody index, respectively. In 18 subjects with diabetic oral glucose tolerance test, GAD65 autoantibody concentrations were higher than in those with normal oral glucose tolerance test (p = 0.02). Subjects with IGT (n = 416) and diabetes (n = 18), i. e. abnormal OGTT (n = 434), had a higher IA-2Ab index compared with those with normal OGTT (p = 0.008). A stepwise multiple logistic regression test showed that the odds ratios for subjects in the highest BMI group to exceed the 95th or 99th GAD65 autoantibody centile were 3.6 (CI 1.4±8.9) and 17.6 (CI 2.6±121.6), respectively. Conclusion/interpretation. GAD65 and IA-2 autoantibodies, are associated with impaired or diabetic glucose tolerance in an adult regional population. This observation together with the association between GAD65 autoantibody concentrations and body mass index indicate a possible relation between islet autoimmunity and beta-cell function abnormalities with obesity and insulin resistance. [Diabetologia (1999)

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“…IA-2 encodes a transmembrane protein of 979 amino acids and features a region homologous to the catalytic domain of receptor type protein tyrosine phosphatases (RT-PTPs) (Lan et al 1994, Rabin et al 1994. It does not demonstrate phosphatase activity in assays with common PTP substrates (Rabin et al 1992, Lan et al 1994, Magistrelli et al 1996. This absence of activity is due to two sequence deviations in the PTP core domain; however, the possibility of a very narrow substrate specificity cannot be ruled out (Magistrelli et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Transmembrane protein tyrosine phosphatase IA-2 (ICA512) is expressed in human midgut carcinoids but is not detectable in normal enterochromaffin cells

Cunningham

Lopez-Egido²,

Janson³

et al. 2000

Journal of Endocrinology

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A potential upregulation of receptor type protein tyrosine phosphatase IA-2 (ICA512) expression was detected by differential display and investigated in midgut carcinoid tumours. Normal intestine tissue and tumour tissue from 13 midgut carcinoid patients were studied by in situ hybridisation using an IA-2 ribonucleotide probe and confocal microscopy using specific IA-2 antibodies. Previously, it had been shown that IA-2 is located in the secretory granules of virtually all neuroendocrine cells. However, we found that IA-2 was not detectable in resting normal enterochromaffin (EC) cells of the small intestine, while high expression of IA-2 mRNA and protein was confirmed in both primary and metastatic carcinoid tissue. This difference in expression was not observed with chromogranin A or serotonin, two secretory granule hormones known to be expressed in EC cells, indicating that IA-2 was seemingly not necessary for the basal production and packaging of these hormones. When comparing patients receiving biotherapy before operation with untreated patients, we found expression of IA-2 to be lower in tumours from patients that had been treated with a combination of -interferon and the somatostatin analogue, octreotide. There was no correlation between IA-2 expression and proliferation rates as measured by immunohistochemistry with antibodies against the Ki 67 antigen. Furthermore, we show that IA-2 is co-localised with serotonin in carcinoid tumours as well as in the pancreatic tumour cell line, BON1, which is interesting as serotonin secretion rate is presumably higher in tumour cells than in resting EC cells. Taken together, these findings may indicate a role for IA-2 in the later stages of the regulated secretory process.

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Cloning and expression of IDDM-specific human autoantigens

Cited by 76 publications

References 0 publications

Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index

Transmembrane protein tyrosine phosphatase IA-2 (ICA512) is expressed in human midgut carcinoids but is not detectable in normal enterochromaffin cells

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