Structural and immunological characterization of hydroxyl radical modified human IgG: Clinical correlation in rheumatoid arthritis

Islam, S. and Mir, A.R. and Arafat, M.Y. and Khan, F. and Zaman, M. and Ali, A. and Moinuddin, . (2018) Structural and immunological characterization of hydroxyl radical modified human IgG: Clinical correlation in rheumatoid arthritis. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 194. pp. 194-201. ISSN 13861425

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Abstract

Structural alterations in proteins under oxidative stress have been widely implicated in the immuno-pathology of various disorders. This study has evaluated the extent of damage in the conformational characteristics of IgG by hydroxyl radical (OH[rad]) and studied its implications in the immuno-pathology of rheumatoid arthritis (RA). Using various biophysical and biochemical techniques, changes in aromatic microenvironment of the IgG and the protein aggregation became evident after treatment with OH[rad]. The SDS-PAGE study confirmed the protein aggregation while far ultraviolet circular dichroism spectroscopy (Far-UV CD) and fourier transform infrared spectroscopy (FTIR) inferred towards the alterations in secondary structure of IgG under OH[rad] stress. Dynamic light scattering showed that the modification increased the hydrodynamic radius and polydispersity of IgG. The free arginine and lysine content reduced upon modification. OH[rad] induced aggregation was confirmed by enhanced thioflavin-T (ThT) fluorescence and red shift in the congo red (CR) absorbance. The study on experimental animals reiterates the earlier findings of enhanced immunogenicity of OH[rad] treated IgG (OH[rad]-IgG) compared to that of native IgG. OH[rad]-IgG strongly interacted with the antibodies derived from the serum of 80 rheumatoid arthritis (RA) patients. The overwhelming and strong tendency of OH[rad]-IgG to bind the antibodies derived from the serum of RA patients points towards the modification of IgG under patho-physiological conditions in RA that generate neo-epitopes and eventually cause the generation of auto antibodies that circulate in the patient sera. Further studies on this aspect may possibly lead to the development of a biomarker for RA.

Item Type: Article
Uncontrolled Keywords: Fenton's reaction; Hydroxyl radical; Immunogenicity; Immunoglobulin G; Rheumatoid arthritis
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Faculty of Medicine > J.N. Medical College > Department of Biochemistry
Depositing User: AMU Library
Date Deposited: 01 Feb 2018 06:05
Last Modified: 01 Feb 2018 06:05
URI: http://ir.amu.ac.in/id/eprint/11048

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