SLE autoantibodies are well recognized by peroxynitrite-modified-HSA: Its implications in the pathogenesis of SLE

Arif, Z. and Neelofar, K and Tarannum, A. and Arfat M.Y., M.Y. and Ahmad S., S and Zaman A., A. and Khan M.A., M.A. and Badar A., A. and Islam S.N., S.N. and Iqubal M.A., M.A. (2018) SLE autoantibodies are well recognized by peroxynitrite-modified-HSA: Its implications in the pathogenesis of SLE. International Journal of Biological Macromolecules, 106. pp. 1240-1249. ISSN 1418130

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder where the role of inflammatory processes in the etiopathogenesis is well documented. Despite extensive research, the trigger for initiation of the disease has not been identified. Peroxynitrite, a strong nitrating/oxidizing agent has been reported in SLE and other autoimmune diseases. In this study, human serum albumin (HSA) was exposed to peroxynitrite for 30 min at 37 °C. The structure of HSA was grossly perturbed when examined by various physico-chemical techniques. Peroxynitrite mediated nitration of HSA was confirmed by LCMS/MS. Furthermore, increase in hydrodynamic radius of peroxynitrite-modified-HSA suggests the attachment of nitro group(s). Aggregation in peroxynitrite-modified-HSA was evident in a TEM scan. Nitration, oxidation, cross linking, aggregation etc conferred immunogenicity on peroxynitrite-modified-HSA. High titre antibodies were elicited in rabbits immunized with peroxynitrite-modified-HSA. Induced antibodies were highly specific for peroxynitrite-modified-HSA but showed considerable binding with other nitrated molecules. Direct binding/inhibition ELISA carried out with autoantibodies in SLE sera showed preferential binding with peroxynitrite-modified-HSA. Anti-nDNA positive IgG from SLE sera showed preference for peroxynitrite-modified-HSA when subjected to immunoassay (direct binding and inhibition) and mobility shift assay. Our results reinforce the role of augmented inflammation in SLE progression. © 2017 Elsevier B.V.

Item Type: Article
Uncontrolled Keywords: Aggregation; IgG; Immunoassay; Peroxynitrite; Systemic lupus erythematosus
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Faculty of Life Sciences > Department of Biochemistry
Depositing User: AMU Library
Date Deposited: 18 Jan 2018 09:43
Last Modified: 18 Jan 2018 09:43
URI: http://ir.amu.ac.in/id/eprint/10785

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