Moinuddin
Aligarh Muslim University, India
Title: Glycoxidative modification of proteins in diabetes results in generation of neo-antigenic epitopes
Biography
Biography: Moinuddin
Abstract
Structural rearrangements and condensations of proteins under glycoxidative stress have been implicated in various pathological disorders. Novel immunological epitopes upon glycoxidatively modifi ed proteins have been discovered and multi-specifi c natural antibodies against them have been identifi ed. In this study, we have probed the glycoxidation of Human Serum Albumin (HSA) and human IgG in diabetes type-2. Glycoxidation was found to perturb the structural integrity of HSA and IgG. It aff ected their aromatic micro-environment and caused the generation of Advanced Glycation End products (AGEs) and aggregate adducts. Generation of N-epsilon-Carboxy Methyl Lysine (CML) was observed under HPLC and LCMS studies. Th e modifi ed proteins showed altered secondary and tertiary structure that would also aff ect their function. Glycoxidation caused disordered or amorphous type aggregation in the modifi ed proteins, as confi rmed by electron microscopy. It enhanced carbonyl content and reduced the free lysine and arginine content. Modifi ed HSA and IgG presented novel antigenic determinants that lead to an aggressive immune response in the immunized rabbits as was evaluated by ELISA studies. Th e antibodies had high affi nity towards the immunogens. Auto-antibodies derived from T2DM patients exhibited strong affi nity towards the modifi ed HSA and IgG in comparison to the respective unmodifi ed proteins. Specifi city of serum antibodies from T2DM patients was further confi rmed by competitive-inhibition ELISA and gel retardation assays. Th e study shows that the neo-antigenic determinants on glycoxidatively modifi ed proteins generate specifi c immune response in diabetes type-2, which may possibly lead to the biomarker development for the disease.