The neoepitopes on methylglyoxal (MG) glycated LDL create autoimmune response; Autoimmunity detection in T2DM patients with varying disease duration

Abstract Aims Non-enzymatic reaction of biomolecules leads to the formation of advanced glycation end products (AGEs). AGEs plays significant role in the pathophysiology of type 2 diabetes mellitus. Methylglyoxal (MG) is a highly reactive carbonyl compound which causes formation of early (ketoamines), intermediate (dicarbonyls) and advanced glycation end products (AGEs). Glycation also results in the generation of free radicals causing structural perturbations which leads to the generation of neo-antigenic epitopes on LDL molecules. The aim of the present study was to investigate whether the modification of LDL results in auto-antibodies generation in type 2 diabetes patients'. Methods The binding affinity of circulating autoantibodies in patients against native and MG modified LDL were assessed as compared with healthy and age-matched controls (n = 50) and T2DM patients with disease duration (DD) 5-15 yrs (n=80) and DD >15 yrs (n=50) were examined by direct binding ELISA. Keyfindings: The high affinity binding were observed in 50% of T2DM with DD 5-15 and 62% of T2DM with DD >15 of patient's sera antibodies to MG-LDL antigen, in comparison to its native analog (P Significance There might be the generation of neoantigenic epitopes on LDL macromoleucle which results in generation of antibodies in T2DM. The prevalence of antibodies was dependent on disease duration.