Autoantibodies in Diabetes

  1. Catherine Pihoker,
  2. Lisa K. Gilliam,
  3. Christiane S. Hampe and
  4. Åke Lernmark
  1. From the Departments of Pediatrics and Medicine, University of Washington, Seattle, Washington
  1. Address correspondence and reprint requests to Dr. Catherine Pihoker, Department of Pediatrics, University of Washington, Seattle, WA 98195. E-mail: catherine.pihoker{at}seattlechildrens.org

Abstract

Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens—GAD65, IA-2, or insulin—signals an autoimmune pathogenesis of β-cell killing. A β-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to β-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitope-specific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally.

Footnotes

  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted May 4, 2005.
    • Received March 4, 2005.
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