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Autoimmunität beim Typ I-Diabetes

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Diabetes mellitus

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Summary

Type I (insulin-dependent) diabetes mellitus is brought about by a chronic autoimmune process directed towards the islets of Langerhans, finally leading to a specific destruction of the beta cells. It has been shown that there exists a genetic susceptibility which is mainly linked with genes of the major histocompatibility complex, namely HLA-DR3, -DR4, and combinations of these HLA specificities, and that distinct DQβ chain alleles confer protection from the disease. The initiating event leading to the autoimmune process still remains unclear. Infiltration of the islets with mononuclear cells is seen in the early stages of the desease and aberrant expression of HLA class II antigens as well as gamma-interferon immunostaining can be exclusively demonstrated on beta cells.

While T cells probably play the key role in the pathogenesis of beta cell destruction, islet cell specific autoantibodies are the most useful markers of autoimmunity in type I diabetes. Cytoplasmic islet cell antibodies (ICA) and/or autoantibodies to the 64-kDa islet cell antigen are positive in 80% – 100% of newly diagnosed cases. ICA are directed towards a glycolipid component of all endocrine islet cells whereas antibodies to the 64-kDa antigen as well as ICA detected by an ELISA recognize a protein. Autoantibodies to insulin (I A A) and/or proinsulin may also be detected in 40–60% of cases before the initiation of insulin therapy.

The above mentioned antibodies may be detected months or years before the abrupt onset of clinical symptoms. This notion has enabled prospective studies of the natural course of the disease in predisposed 1st degree relatives of type I diabetic patients and in epidemiological screening programmes. In otherwise healthy relatives high levels of ICA, the presence of complement-fixing ICA, and the detection of IAA by radioimmunoassays indicate a high risk for future development of type I diabetes. A blunted first-phase insulin response to i.v. glucose appears to be the most sensitive marker for an irreversible metabolic deterioration. By a better understanding of the natural course of the disease and the associated immune process it will be possible to proceed with early immune intervention trials aiming at interruption of the autoimmune beta cell destruction.

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Authors
  1. W. A. Scherbaum
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Editors and Affiliations

  1. Medizinische Klinik III und Poliklinik, Klinikum der Justus-Liebig-Universität Gießen, Rodthohl 6, 6300, Gießen, Deutschland

    Reinhard G. Bretzel

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© 1990 Springer-Verlag · Heidelberg

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Scherbaum, W.A. (1990). Autoimmunität beim Typ I-Diabetes. In: Bretzel, R.G. (eds) Diabetes mellitus. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74610-9_2

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  • DOI: https://doi.org/10.1007/978-3-642-74610-9_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74611-6

  • Online ISBN: 978-3-642-74610-9

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