Failure to detect anti-idiotypic antibodies in the autoimmune response to IA-2 in Type 1 diabetes

Richardson, Carolyn C. and McLaughlin, Kerry A. and Brown, Thomas J. and Morgan, Diana and Feltbower, Richard and Powell, Michael and Furmaniak, Jadwiga and Rees Smith, Bernard and Christie, Michael R. (2013) Failure to detect anti-idiotypic antibodies in the autoimmune response to IA-2 in Type 1 diabetes. Autoimmunity, 46 (6). pp. 375-381. ISSN 0891-6934

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Item Type:Article
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Abstract

The concept that immune responses to self antigens are regulated by anti-idiotypic networks has attracted renewed interest following reports of circulating factors within IgG fractions of serum that impair detection of autoantibodies with autoantigen. Thus, preclearance of sera with bead-immobilised monoclonal autoantibodies to the Type 1 diabetes autoantigen GAD65, or prebinding of serum antibodies to protein A Sepharose prior to addition of antigen, increases immunoreactivity detected in serum samples consistent with the trapping on the beads of anti-idiotypic antibodies that block antibody binding to the autoantigen. The aim of this study was to investigate the presence of anti-idiotypic antibodies to another major target of autoantibodies in Type 1 diabetes, IA-2. As previously observed for GAD65, preadsorption of serum samples with immobilised monoclonal IA-2 autoantibody, or prebinding to protein A Sepharose, resulted in substantial increases in subsequent immunoprecipitation of radiolabeled IA-2 in a proportion of samples. However, control experiments indicated that the increases seen on pre-incubation with immobilized autoantibodies were caused by displacement of the antibody by serum IgG, whereas impaired detection of immunoreactivity in liquid-phase radiobinding assays was the result of formation of insoluble complexes that bind poorly to protein A. The results emphasise the importance of direct demonstration of specific binding of antibodies to the idiotype in the study of idiotypic networks in autoimmunity. Variability between patients in formation of insoluble immune complexes has implications for the design and standardization of autoantibody assays for diabetes prediction. © 2013 Informa UK Ltd.

Keywords:antiidiotypic antibody, glutamate decarboxylase 65, IA 2 monoclonal antibody, immunoglobulin F(ab) fragment, immunoglobulin G, monoclonal antibody, protein A, sepharose, unclassified drug, adolescent, adsorption, adult, article, autoimmunity, blood sampling, child, clinical article, human, human tissue, immunoglobulin blood level, immunoprecipitation, immunoreactivity, insulin dependent diabetes mellitus, school child, Adolescent, Antibodies, Anti-Idiotypic, Antigen-Antibody Complex, Autoantibodies, Child, Preschool, Diabetes Mellitus, Type 1, Female, Glutamate Decarboxylase, Humans, Male, Protein Binding, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Staphylococcal Protein A, Young Adult
Subjects:C Biological Sciences > C550 Immunology
Divisions:College of Science > School of Life Sciences
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ID Code:18112
Deposited On:05 Aug 2015 13:23

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