Combined screening for antoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM

Seissler, J., Morgenthaler, N. G., Achenbach, P. , Lampeter, E .F., Glawe, D., Payton, M., Christie, Michael and Scherbaum, W. A. (1996) Combined screening for antoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM. Diabetologia, 39 (11). pp. 1351-1356. ISSN 0012-186X

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To determine the value of antibodies to the intracytoplasmic domain of the tyrosine phosphatase IA-2 (anti-IA-2 ic) and glutamic acid decarboxylase (GADA) for identification of subjects at risk for insulin-dependent diabetes mellitus (IDDM) we investigated 1238 first degree relatives of patients with IDDM for the presence of anti-IA-2 ic and GADA and compared the results with cytoplasmic islet cell antibodies (ICA). Anti-IA-2 ic were observed in 54 (4.4 %) first degree relatives, in 51 of 86 (59.3 %) ICA positive relatives and in 3 of 4 individuals who developed overt IDDM within a follow-up period of 1 to 28 months. GADA were found in 78 of 1238 (6.3 %) first degree relatives. They were detected in 22 of 35 (62.9 %) sera with ICA alone and in 1 of 3 subjects with anti-IA-2 ic in the absence of ICA. Of the 1238 subjects 37 (3.0 %) sera were positive for all three antibodies. Both anti-IA-2 ic and GADA were positively correlated with high levels of ICA. Anti-IA-2 ic and GADA were detected in 39.1 and 47.8 % of subjects with ICA of less than 20 Juvenile Diabetes Foundation units (JDF-U) but in 66.7 and 76.2 % of individuals with ICA of 20 JDF-U or more, respectively (p < 0.05). The levels of ICA and GADA in first degree relatives with at least one additional marker were significantly higher than in subjects with ICA alone (p < 0.005) or GADA alone (p < 0.03). The combination of anti-IA-2 ic and GADA identified 84.9 % of all ICA positive subjects and 93.7 % of individuals with high level ICA (≥ 20 IDF-U). All 4 individuals who progressed to IDDM had either IA-2 ic or GADA. Our data indicate that primary screening for anti-IA-2 ic and GADA provides a powerful approach with which to identify subjects at risk for IDDM in large-scale population studies which may represent the basis for the design of new intervention strategies.

Keywords:autoantibody, biological marker, glutamate decarboxylase, pancreas islet cell antibody, protein tyrosine phosphatase, recombinant protein, adolescent, adult, age distribution, article, child, comparative study, family, female, fluorescent antibody technique, follow up, human, immunology, infant, insulin dependent diabetes mellitus, male, middle aged, pancreas islet, preschool child, prevalence, radioassay, risk factor, autoimmunity, controlled study, familial disease, major clinical study, priority journal, Adolescent, Autoantibodies, Biological Markers, Child, Preschool, Diabetes Mellitus, Type 1, Fluorescent Antibody Technique, Indirect, Follow-Up Studies, Humans, Islets of Langerhans, Protein-Tyrosine-Phosphatase, Radioligand Assay, Recombinant Proteins, Risk Factors
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18153
Deposited On:31 Jul 2015 10:43

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