Studies on glycoxidatively modified human IgG: Implications in immuno-pathology of type 2 diabetes mellitus

Islam, S and Moinuddin, . and Mir, A.R. and Arfat, M.Y. and Alam, K. and Ali, A. (2017) Studies on glycoxidatively modified human IgG: Implications in immuno-pathology of type 2 diabetes mellitus. International Journal of Biological Macromolecules, 104. p. 19. ISSN 1418130

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Abstract

Structural rearrangements and condensations of proteins under hyperglycemic stress have been implicated in various pathological disorders. This study aims to probe the role of methylglyoxal (MG) modified human immunoglobulin G (MG-IgG) in immuno-pathology of type 2 diabetes mellitus (T2DM). MG was found to perturb the structural integrity of IgG, affect its aromatic micro-environment and cause the generation of advanced glycation end products (AGEs) and aggregate adducts. It liberated the hydrophobic pockets of the protein, reduced its β pleated sheet structure and affected its tertiary conformation. Transition from β sheet to α helix and random coil was also observed in IgG upon modification by MG. It acted with strong oxidative potential and caused oligomerisation and disordered or amorphous type aggregation in the modified protein. Modified IgG had a cytotoxic and genotoxic impact. The MG modified IgG presented novel antigenic determinants that lead to an aggressive immune response. The antibodies had high affinity towards the immunogen. Auto-antibodies derived from T2DM patients exhibited strong affinity towards the modified IgG in comparison to the unmodified protein. Specificity of serum antibodies from T2DM patients was further confirmed by competitive-inhibition ELISA. The potential role of MG-IgG in the immunopathogenesis of T2DM has been discussed.

Item Type: Article
Uncontrolled Keywords: Autoimmunity; Glycation; Immunoglobulin G; Methylglyoxal; Type 2 diabetes mellitus
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Faculty of Life Sciences > Department of Biochemistry
Depositing User: AMU Library
Date Deposited: 25 Jan 2018 09:30
Last Modified: 25 Jan 2018 09:30
URI: http://ir.amu.ac.in/id/eprint/10968

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