Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA

Khan, M.A. and Alam, K. and Mehdi, S.H and Rizvi, M.M.A. (2017) Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA. Archives of Biochemistry and Biophysics, 635. pp. 8-16. ISSN 39861

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Abstract

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE.

Item Type: Article
Uncontrolled Keywords: Autoimmunity; Comet assay; Genotoxicity; Human placental DNA; Peroxynitrite
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Faculty of Life Sciences > Department of Biochemistry
Depositing User: AMU Library
Date Deposited: 25 Jan 2018 07:54
Last Modified: 25 Jan 2018 07:54
URI: http://ir.amu.ac.in/id/eprint/10967

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