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Exploring the idiotypes of insulin antibodies as markers for remission in Type 1 diabetes
Author(s) -
Devendra D.,
Galloway T. S.,
Horton S. J.,
Wilkin T. J.
Publication year - 2004
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2004.01344.x
Subject(s) - medicine , insulin , autoantibody , diabetes mellitus , antibody , type 1 diabetes , idiotype , immunogenicity , endocrinology , immunology , gastroenterology , monoclonal antibody
Aims Complete or partial remission can occur in newly diagnosed Type 1 diabetes patients. We created idiotype‐specific reagents to explore the idiotypes of insulin antibodies (IA) in a patient in remission, and to compare with a patient who was not. Methods Phage display was used to create a library of phagotopes specific to insulin binding in four sera. Sera from a Type 1 diabetes subject deemed to have undergone remission were taken at diagnosis and again during remission. Sera from a non‐remitter were taken at diagnosis and after 3 months on insulin. Phagotopes from the four sera were randomly selected and tested for insulin specificity in a radiobinding assay by using sera from remitters and non‐remitters. Results IA‐binding phagotope selected from serum during remission displaced insulin binding in all nine IA + remitters and all 10 IA + non‐remitters. IA‐binding phagotope selected from the non‐remission patient (3 months after insulin therapy) displaced insulin binding in 8/9 IA + remitters and 8/10 IA + non‐remitters. The consensus peptide sequences adduced from the phages were identical for both these phagotopes. Phagotopes derived from insulin autoantibody‐positive individuals at diagnosis were unable to displace insulin binding in the IA + sera 3 months later, whether in remission or not. Conclusions We have established the principle of using phage display in the investigation of insulin antibodies during remission in Type 1 diabetes. The immunological characteristics of IA 3 months after the introduction of insulin treatment were different from those at diagnosis of Type 1 diabetes (IAA). Using phage display technology, it was not possible to distinguish insulin antibodies according to remission status.