IA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients and help predict impending diabetes in their siblings

Gorus, F. K., Goubert, P., Semakula, C. , Vandewalle, C. L., De Schepper, J., Scheen, A., Christie, Michael R. and Pipeleers, D. G. (1997) IA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients and help predict impending diabetes in their siblings. Diabetologia, 40 (1). pp. 95-99. ISSN 0012-186X

Full content URL: http://link.springer.com/article/10.1007%2Fs001250...

Documents
IA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients and help predict impending diabetes in their siblings

Request a copy
[img] PDF
art%3A10.1007%2Fs001250050648.pdf - Whole Document
Restricted to Repository staff only

47kB
Item Type:Article
Item Status:Live Archive

Abstract

IA-2 has been identified as an autoantigen that is recognized by immunoglobulins from insulin-dependent diabetic (IDDM) patients. Using a liquid phase radiobinding assay, we performed an IA-2-autoantibody (IA-2-Ab) assay in 474 IDDM patients and 482 non-diabetic control subjects aged 0–39 years. IA-2-Ab were detected in 58 % of the patients and 0.8 % of control subjects. Their prevalence in patients was lower than that of islet cell autoantibodies (ICA; 73 %) or glutamic acid decarboxylase (Mr 65 kDa)-autoantibodies (GAD65-Ab; 82 %) but higher than that of insulin autoantibodies (IAA; 42 %). IA-2-Ab were more frequent in patients under age 20 years (70 %) than between 20 and 40 years (45 %; p < 0.001). In the whole IDDM group, 92 % of patients were positive for at least one of the three molecular assays, which is higher than the positivity for the ICA assay (73 %). Only 1 % was negative in the molecular assays and positive in the ICA assay. IA-2-Ab levels were positively correlated with ICA titres (p < 0.001) and HLA DQ A1*0301 – DQ B1*0302 (p < 0.003) by multivariate analysis. In a group of 481 non-diabetic siblings (age 0–39 years) of IDDM patients only 7 were IA-2-Ab positive (1.5 %). All seven were under age 20 years and positive for at least two other autoantibodies and for DQ A1*0301 – DQB1*0302. Four of these seven developed IDDM during the 6–70-month follow-up period. The positive predictive value of IA-2-Ab (57 %) was higher than that of ICA, GAD65-Ab or IAA alone, or in combination (≤ 20 %) but these calculations are restricted by the relatively short observation period and the small number of cases. The only IA-2-Ab-negative case of pre-diabetes was also negative for IAA and GAD65-Ab, while it was strongly positive for ICA. In conclusion, IA-2-Ab show a high diagnostic specificity for IDDM and are predictive markers of impending diabetes in siblings of patients. In combination with other molecular antibody assays they may replace ICA testing in future. Our data also indicate that other autoantibodies than IA-2-Ab, GAD65-Ab and IAA contribute to ICA

Keywords:autoantibody, insulin antibody, protein tyrosine phosphatase, adolescent, adult, article, child, controlled study, genetic susceptibility, human, insulin dependent diabetes mellitus, major clinical study, prediction, priority journal, Adolescent, Age of Onset, Autoantibodies, Belgium, Biological Markers, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Female, Glutamate Decarboxylase, HLA-D Antigens, Humans, Islets of Langerhans, Male, Nuclear Family, Prevalence
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
Related URLs:
ID Code:18149
Deposited On:31 Jul 2015 10:27

Repository Staff Only: item control page