Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Åke Lernmark

Principal investigator

Default user image.

Molecular biology of IDDM

Author

  • Å Lernmark

Summary, in English

The clinical onset of insulin-dependent diabetes is associated with several autoimmune phenomena including islet cell antibodies, glutamic acid decarboxylase (the GAD65 isoform) autoantibodies (GAD65Ab) as well as insulin autoantibodies. The molecular cloning of these autoantigens has permitted the development of precise and reproducible antibody immunoassays to identify marker-positive patients and control subjects. Among patients with new-onset diabetes about 70% were GAD65Ab positive compared to 1.5% among control subjects while 46% of patients had IAA compared to 1% among control subjects. The autoreactive sites or epitopes of GAD65 and insulin remain to be determined. The disease association with HLA on chromosome 6 may help to define the epitope specificity of the autoimmune reaction. Recent data suggest that 95% of new-onset IDDM children (0-15 years of age) are positive for either DQ2, DQ8 or both compared to about 50% of healthy control subjects. HLA-DQ6 is negatively associated with the disease. Both HLA-DQ2 and DQ8 therefore seem to be necessary, but not sufficent for diabetes. Molecular modelling suggests comparable physicochemical properties of DQ2 and DQ8 but are widely different from DQ6. In 1984, the conclusion was that molecular cloning of the genes for the autoantigens, antibodies, T-cell receptors, as well as HLA class I and II molecules associated with diabetes are essential for analysing the components which control the development of pancreatic beta-cell autoimmunity. In 1994, autoantigens and HLA molecules have been cloned and recombinant reagents developed to be used in experiments aimed at testing whether it will be possible to predict IDDM. Our understanding of immune autoreactivity is, however, still inadequate and remains a major challenge to future Minkowski Award hopefuls.

Publishing year

1994-09-01

Language

English

Publication/Series

Diabetologia

Volume

37

Issue

2 Supplement

Document type

Journal article

Publisher

Springer

Keywords

  • chromosome 6
  • GAD65
  • GAD67
  • glutamic acid decarboxylase (GAD) autoantibodies
  • HLA
  • insulin autoantibodies
  • Islet cell antibodies
  • major histocompatibility complex

Status

Published

ISBN/ISSN/Other

  • ISSN: 0012-186X