Advanced Glycation End Products (AGEs) Damaged IgG, a Target for Circulating Autoantibodies in Patients with Type 1 Diabetes Mellitus

Abstract

The role of advanced glycation end products (AGEs)-damaged immunoglobulin G (AGE-IgG) in type 1 diabe- tes has been investigated in the present study. IgG was isolated from the normal humans and was subjected to in vitro gly- cation with glucose. The AGEs caused extensive damaged to IgG. The AGE-IgG was found to be highly immunogenic in rabbits as compared to native IgG. The binding characteristics of circulating autoantibodies in type 1 diabetes mellitus (DM) patients against native and AGE-IgG were assessed. Type 1 DM patients (n=31) were examined by ELISA and their results were compared with healthy age-matched human controls (n=22). High degree of specific binding by 61.3 % of DM sera autoantibodies towards AGE-IgG was observed, in comparison to its native analog (p< 0.05). Sera from those type 1 DM patients having smoking history, high aging with high degree of disease showed substantially stronger binding to AGE-IgG over native IgG in particular. IgG from type 1 DM patients (DM-IgG) contained higher levels of carbonyls as compared to normal human subjects (normal-IgG) (p<0.001). Collectively, the AGEs modification of IgG causes pertur- bations, resulting in the generation of neo-epitopes, and making it a potential immunogen. The IgG modified with AGEs may be one of the factors for the induction of circulating type 1 diabetes autoantibodies.