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.

References

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