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

Abstract

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.

Immunological Functions of Oxidized Human Immunoglobulin G in Type 1 Diabetes Mellitus: Its Potential Role in Diabetic Smokers as a Biomarker of Elevated Oxidative Stress

“…We and others have reported the presence of elevated levels of oxidized protein products (advanced oxidation protein products) such as oxidized plasma protein in patients with various diseases [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Furthermore, ROS modified IgG is highly immunogenic in rabbits, and the antigenic specificity of affinity purified anti-ROS-IgG antibodies and anti-IgG antibodies suggest that induced antibodies are immunogen-specific.…”

Production of Cross-Reactive Autoantibody Binding to Bovine Serum Albumin in the D-Galactose-Induced Aging Mouse Model

“…AGEs could be an example of the latter case, although the direct correlation among excessive carbohydrates, AGEs and their autoantibodies has not been verified to date. Previous studies have demonstrated antibody production in response to CML-BSA in diabetic human patients (Shibayama et al, 1999) as well as higher antigenicity of AGE-IgG than IgG (Rasheed et al, 2009).…”

Glycoxidation of histone proteins in autoimmune disorders

“…Reports suggest role of AGEs in the activation of inflammatory signalling cascades and in the pathogenesis of diabetic complications [61,77]. Autoimmune response to advanced glycosylation end-products has also been widely reported with B lymphocytes playing a major pathogenic role by the generation of autoantibodies [78].…”