Exploring the idiotypes of insulin antibodies as markers for remission in Type 1 diabetes

• Published in: Diabetic medicine 2004-12, Vol.21 (12), p.1316-1324
• Main Authors: Devendra, D., Galloway, T. S., Horton, S. J., Wilkin, T. J.
• Format: Article
• Language: English
• Subjects: Adolescent; Antibody Specificity; Autoantibodies - immunology; Biological and medical sciences; Biomarkers - blood; Case-Control Studies; Child; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; honeymoon period; Humans; Immunoglobulin Idiotypes - blood; Insulin - immunology; insulin antibody; insulin autoantibody; Male; Medical sciences; metabolic remission; Middle Aged; Peptide Library; phage display; Radioligand Assay; Remission Induction; Type 1 diabetes
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2004.01344.x

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.