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Horm Metab Res 2002; 34(4): 186-191
DOI: 10.1055/s-2002-26708
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

IA-2 Autoantibodies Restricted to the IgG4 Subclass are Associated with Protection from Type 1 Diabetes

J.  Seissler 1 , K.  Eikamp 1 , M.  Schott 2 , W.  A.  Scherbaum 1, 2 , DENIS . Study Group 1
  • 1 German Diabetes Research Institute, University of Düsseldorf, Germany
  • 2 Department of Endocrinology, University of Düsseldorf, Germany
Further Information

Publication History

18 September 2001

10 January 2002

Publication Date:
30 April 2002 (online)

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Abstract

The tyrosine phosphatase-like protein IA-2 is a major target antigen for autoantibodies in the preclinical period of type 1 diabetes. In this study, we examined whether immunoglobulin isotypes and IgG subclass specific autoantibodies directed at IA-2 discriminate between children at risk of type 1 diabetes who progressed to diabetes vs. those who remained diabetes-free. IgG1-4, IgA and the IgE-specific IA-2 antibody (IA-2A) were measured by radioligand assays in 50 patients with type 1 diabetes and 41 ICA-positive siblings of patients with type 1 diabetes who were followed for diabetes development. Of 41 siblings, 32 were positive for IA-2A; of these, 59 % had IA-2 IgG1, 59 % IgG4, 16 % IgG3, 9 % IgG2, 16 % IgA and 13 % IgE antibodies. IA-2 IgG1 was the dominant isotype in prediabetic children (n = 14, 86 % positive) and patients with type 1 diabetes (98 % positive) whereas only 7 of 18 (39 %) non-progressors had antibodies of this isotype. In subjects that remained diabetes-free, a significantly higher frequency of IA-2 IgG4 in the absence of IgG1 was observed (50 %) compared to progressors (7 %) and patients with type 1 diabetes (0 %). Life-table analysis revealed that IA-2A restricted to IgG4 correlated with protection from type 1 diabetes (p < 0.003). In contrast, IA-2 IgG2, IgG3, IgE and IgA did not differ significantly between study groups. Our findings suggest that the measurement of IA-2 IgG1 and IgG4 subclass antibodies can serve as surrogate marker to discriminate between antibody positive subjects at high or low risk for rapid development of diabetes.

Key words

IA-2 - Autoantibodies - Isotype - Prediction - Type 1 Diabetes

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J. Seissler, M.D.

German Diabetes Research Institute · University of Düsseldorf

Auf'm Hennekamp 65 · 40225 Düsseldorf · Germany

Fax: + 49 (211) 338 26 62

Email: seissler@ddfi.uni-duesseldorf.de

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