title: Neo-epitopes on methylglyoxal modified human serum albumin lead to aggressive autoimmune response in diabetes.
abstract: Glyco-oxidation of proteins has implications in the progression of diabetes type 2. Human serum albumin is prone to glyco-oxidative attack by sugars and methylglyoxal being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. This study has probed the methylglyoxal mediated modifications of HSA, the alterations in its immunological characteristics and possible role in autoantibody induction. We observed an exposure of chromophoric groups, loss in the fluorescence intensity, generation of AGEs, formation of cross-linked products, decrease in α-helical content, increase in hydrophobic clusters, FTIR band shift, attachment of methylglyoxal to HSA and the formation of N(ε)-(carboxyethyl) lysine in the modified HSA, when compared to the native albumin. MG-HSA was found to be highly immunogenic with additional immunogenicity invoking a highly specific immune response than its native counterpart. The binding characteristics of circulating autoantibodies in type 2 diabetes mellitus (DM) patients showed the generation of anti-MG-HSA auto-antibodies in the these patients, that are preferentially recognized by the modified albumin. We propose that MG induced structural perturbations in HSA, result in the generation of neo-epitopes leading to an aggressive auto-immune response and may contribute to the immunopathogenesis of diabetes type 2 associated complications.
authors: Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors: Jyoti
authors: Department of Biotechnology, Government Degree College, Baramulla, Jammu and Kashmir, India.
authors: Abdul Rouf
authors: AR
authors: Mir
authors: Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors: Safia
authors: S
authors: Habib
authors: Rajeev Gandhi Centre for Diabetes, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors: Sheelu Shafiq
authors: SS
authors: Siddiqui
authors: Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors: Asif
authors: A
authors: Ali
authors: Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India. Electronic address: moin_u@rediffmail.com.
authors: Moinuddin
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008239:Lysine / Q000378:metabolism; D008297:Male; D011487:Protein Conformation; D011765:Pyruvaldehyde / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000939:Epitopes; D007074:Immunoglobulin G; D012709:Serum Albumin; D011765:Pyruvaldehyde; D008239:Lysine
keywords: Advance glycation end products (AGEs); Autoimmunity; Diabetes type 2; Human serum albumin; Methylglyoxal; N(ε)-(carboxyethyl)lysine