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Åke Lernmark

Principal investigator

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A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

Author

  • C. E. Grubin
  • T. Daniels
  • B. Toivola
  • M. Landin-Olsson
  • W. A. Hagopian
  • L. Li
  • A. E. Karlsen
  • E. Boel
  • B. Michelsen
  • Å Lernmark

Summary, in English

Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p<0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14 year-old patients (n=105), and matched, healthy control subjects (n=157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD.

Department/s

  • Diabetes lab
  • Medicine, Lund

Publishing year

1994-04-01

Language

English

Pages

344-350

Publication/Series

Diabetologia

Volume

37

Issue

4

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • autoimmunity
  • diabetes mellitus
  • diagnostic accuracy
  • Glutamic acid decarboxylase
  • islet cell antibodies
  • receiver-operating characteristic plot

Status

Published

Research group

  • Diabetes lab

ISBN/ISSN/Other

  • ISSN: 0012-186X