Exploring the idiotypes of insulin antibodies as markers for remission in Type 1 diabetes.
OBJECTIVE
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.
Devendra
D
D
Department of Endocrinology & Metabolism, Peninsula Medical School, Plymouth campus, Plymouth, UK. devasenan.devendra@uchsc.edu
Galloway
T S
TS
Horton
S J
SJ
Wilkin
T J
TJ
D000293:Adolescent; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000097:blood*; D007328:Insulin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D011869:Radioligand Assay; D012074:Remission Induction
D001323:Autoantibodies; D015415:Biomarkers; D007130:Immunoglobulin Idiotypes; D007328:Insulin; D019151:Peptide Library