Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease?


Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.

Publication DOI:
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: NOTICE: this is the author’s version of a work that was accepted for publication in Autoimmunity reviews. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Griffiths, Helen R. (2008). Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease? Autoimmunity reviews, 7 (7), pp. 544-549. DOI 10.1016/j.autrev.2008.04.013
Uncontrolled Keywords: reactive oxygen species,reactive nitrogen species,protein oxidation,autoantigen,neo-antigenic determinant,DNA oxidation,Immunology,Immunology and Allergy
Publication ISSN: 1873-0183
Last Modified: 17 Jul 2024 07:02
Date Deposited: 11 Mar 2019 17:48
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2008-07
Authors: Griffiths, Helen R. (ORCID Profile 0000-0002-2666-2147)

Export / Share Citation


Additional statistics for this record