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Åke Lernmark

Principal investigator

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Recombinant glutamic acid decarboxylase (representing the single isoform expressed in human islets) detects IDDM-associated 64,000-Mr autoantibodies

Author

  • Allan E. Karlsen
  • William A. Hagopian
  • Jacob S. Petersen
  • Esper Boel
  • Thomas Dyrberg
  • Catherine E. Grubin
  • Birgitte K. Michelsen
  • Ole D. Madsen
  • Åke Lernmark

Summary, in English

GAD is an autoantigen in IDDM. Molecular cloning and specific antibodies allowed us to demonstrate that only the lower Mr GAD64 isoform is expressed in human islets, in contrast to human brain, rat islets, and rat brain, all of which express both GA064 and GAD67. Expression of the human islet GAD64 isoform in COS-7 and BHK cells resulted in an enzymatically active rGAD64, which is immunoreactive with diabetic sera comparable with that of the islet 64,000-Mr autoantigen. Immunoprecipitation analyses showed that 21/28 (75%) IDDM sera had rGAD64 antibodies compared with only 1/59 (1.7%) of the healthy control sera. In immunoblot analyses, an SMS serum - but only 1/10 randomly selected IDDM sera - recognized the blotted rGAD64 without relation to immunoprecipitation titers. In conclusion, only the GAD64 isoform is expressed in human islets, in contrast to rat islets, which also express the GAD67 isoform. The immunological properties of human rGAD64 are comparable with the native 64,000-Mr islet autoantigen, allowing further studies of the immunopathogenesis of IDDM.

Publishing year

1992-01-01

Language

English

Pages

1355-1359

Publication/Series

Diabetes

Volume

41

Issue

10

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

ISBN/ISSN/Other

  • ISSN: 0012-1797