The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes

Research output: Contribution to journalArticle

Abstract

Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n = 238) and first-degree relatives (FDRs) of T1D patients (n = 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n = 54) and Stiff Person Syndrome patients (n = 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab.

Details

Authors
  • Shilpa Oak
  • Lisa K. Gilliam
  • Mona Landin-Olsson
  • Carina Törn
  • Ingrid Kockum
  • Christina R. Pennington
  • Merrill J. Rowley
  • Michael R. Christie
  • J. Paul Banga
  • Christiane S. Hampe
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine
  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)5471-5476
JournalProceedings of the National Academy of Sciences
Volume105
Issue number14
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes