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Åke Lernmark

Principal investigator

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Autoantibodies in IDDM primarily recognize the 65,000-Mr rather than the 67,000-Mr isoform of glutamic acid decarboxylase

Author

  • William A. Hagopian
  • Birgitte Michelsen
  • Allan E. Karlsen
  • Fleming Larsen
  • Alistar Moody
  • Catherine E. Grubin
  • Rachel Rowe
  • Jacob Petersen
  • Robert Mcevoy
  • Åke Lernmark

Summary, in English

Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD65 and GAD67 autoantibody targets, but human islets express only GAD65, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves β-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healthy control subjects for antibodies to recombinant human islet GAD65, rat islet GAD67, or human insulinoma/ cerebellum GAD67, each expressed separately in hamster fibroblasts. By using immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and densitometric fluorogram scanning, 132 of 190 (70%) of new IDDM patients had GAD65 autoantibodies, whereas only 17 of 190 (9%) had antibodies to rat GAD67 (P < 0.001). Of healthy control subjects, 2 of 51 (3.9%) and 1 of 51 (1.9%) had antibodies to GAD65 and GAD67, respectively. All 17 GAD67 antibody-positive patients also had GAD65 antibodies; 14 of 17 with greater GAD65 than GAD67 index. Control studies showed comparable reactivity between recombinant rat and human GAD67 and between different subcellular preparations of recombinant GAD67 of either species. In conclusion, only GAD65 is expressed in human islets, the autoantibody response is primarily to this isoform, and GAD67 antibodies add little to IDDM detection.

Publishing year

1993-01-01

Language

English

Pages

631-636

Publication/Series

Diabetes

Volume

42

Issue

4

Document type

Journal article

Publisher

American Diabetes Association Inc.

Status

Published

ISBN/ISSN/Other

  • ISSN: 0012-1797