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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 14; pp. 5471 - 5476
• Main Authors: Oak, Shilpa, Gilliam, Lisa K, Landin-Olsson, Mona, Törn, Carina, Kockum, Ingrid, Pennington, Christina R, Rowley, Merrill J, Christie, Michael R, Banga, J. Paul, Hampe, Christiane S
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08-04-2008; National Acad Sciences
• Subjects: Annan klinisk medicin; Anti idiotypic antibodies; Antibodies; Antibodies, Anti-Idiotypic - blood; Antigens; Autoantibodies; Autoantibodies - blood; Autoimmune diseases; B lymphocytes; Biological Sciences; Case-Control Studies; Clinical Medicine; Diabetes; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - immunology; Endocrinology; Endocrinology and Diabetes; Endokrinologi och diabetes; Epitopes; Family Health; Glutamate Decarboxylase - immunology; Humans; Immune system; Immunology; Klinisk medicin; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Other Clinical Medicine; Radioimmunoassay; Stiff-Person Syndrome; T lymphocytes; Type 1 diabetes mellitus; Type 2 diabetes mellitus
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0800578105

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.