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 diabetes has been investigated in the present study. IgG was isolated from the normal humans and was subjected to in vitro glycation 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 perturbations, 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.

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