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

Oak, Shilpa and Gilliam, Lisa K. and Landin-Olsson, Mona and Torn, Carina and Kockum, Ingrid and Pennington, Christina R. and Rowley, Merrill J. and Christie, Michael R. and Banga, J. Paul and Hampe, Christiane S. (2008) The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes. Proceedings of the National Academy of Sciences of the United States of America, 105 (14). pp. 5471-5476. ISSN 0027-8424

Full content URL: http://www.pnas.org/content/105/14/5471.full

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

Request a copy
[img] PDF
5471.full.pdf - Whole Document
Restricted to Repository staff only

370kB
Item Type:Article
Item Status:Live Archive

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. © 2008 by The National Academy of Sciences of the USA.

Keywords:antiidiotypic antibody, autoantibody, epitope, glutamate decarboxylase 65 antibody, monoclonal antibody, adolescent, adult, antigen binding, article, controlled study, enzyme binding, enzyme linked immunosorbent assay, female, human, insulin dependent diabetes mellitus, male, normal human, priority journal, radioimmunoassay, relative, stiff man syndrome, Antibodies, Anti-Idiotypic, Autoantibodies, Case-Control Studies, Diabetes Mellitus, Type 1, Family Health, Glutamate Decarboxylase, Humans, Stiff-Person Syndrome
Subjects:C Biological Sciences > C550 Immunology
Divisions:College of Science > School of Life Sciences
Related URLs:
ID Code:18117
Deposited On:05 Aug 2015 14:11

Repository Staff Only: item control page