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

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Abstract

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.

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  • autoimmunity_reviews.pdf

    Rights statement: 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

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Original languageEnglish
Pages (from-to)544-549
Number of pages6
JournalAutoimmunity Reviews
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 2008

Bibliographic note

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

    Keywords

  • reactive oxygen species, reactive nitrogen species, protein oxidation, autoantigen, neo-antigenic determinant, DNA oxidation

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