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

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.

Gilliam, Lisa K. (author)
Landin-Olsson, MonaLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-mla (author)
Törn, CarinaLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups(Swepub:lu)med-cto (author)
Kockum, IngridKarolinska Institutet (author)
Pennington, Christina R. (author)
Rowley, Merrill J. (author)
Christie, Michael R. (author)
Banga, J. Paul (author)
Hampe, Christiane S. (author)
Medicin, LundSektion II (creator_code:org_t)

In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences105:14, s. 5471-54761091-64900027-8424

By the author/editor: Oak, Shilpa; Gilliam, Lisa K.; Landin-Olsson, M ...; Törn, Carina; Kockum, Ingrid; Pennington, Chri ...; show more...; Rowley, Merrill ...; Christie, Michae ...; Banga, J. Paul; Hampe, Christian ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Other Clinical M ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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