Consequence of neo-antigenicity of the ‘altered self’

Post-translational modifications play a central role in determining the function of proteins. Such protein modifications come in a great variety of guises, and include phosphorylation, proteolysis, glycosylation, citrullination and oxidative modifications. In relation to inflammatory autoimmune dise...

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Bibliographic Details
Published in:Rheumatology (Oxford, England) England), 2008-05, Vol.47 (5), p.567-571
Main Authors: Eggleton, P., Haigh, R., Winyard, P. G.
Format: Article
Language:English
Subjects:
Anti-phospholipid syndrome
Antigen-Antibody Reactions
Apoptosis
Autoantibodies - metabolism
Autoantibody
Autoantigens - genetics
Autoantigens - metabolism
Autoimmune Diseases - etiology
Autoimmune Diseases - metabolism
Biological and medical sciences
Cell Death
Citrullination
Diseases of the osteoarticular system
Genetic Predisposition to Disease
Humans
Inflammation
Medical sciences
Miscellaneous. Osteoarticular involvement in other diseases
Neo-antigenicity
Oxidized low-density lipoprotein
Post-translational modification
Protein oxidation
Protein Processing, Post-Translational
Proteomics
Rheumatic diseases
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Summary:Post-translational modifications play a central role in determining the function of proteins. Such protein modifications come in a great variety of guises, and include phosphorylation, proteolysis, glycosylation, citrullination and oxidative modifications. In relation to inflammatory autoimmune diseases, some post-translational modifications appear to result in the generation of new antigens, and hence autoantibodies. Examples include: the induction of peptide immunogenicity by the spontaneous conversion of aspartic acid residues to isoaspartic acid; granzyme B-mediated cleavage of SLE autoantigens; the oxidative modification—on the surface of apoptotic cells—of lipids and proteins, rendering them immunogenic; and the presence of antibodies to oxidatively modified type II collagen and C1q in RA and SLE patients, respectively. The measurement of autoantibodies to citrullinated proteins has been verified as a very useful diagnostic tool in RA. Proteomics techniques, in principle, allow the detection of all types of in vivo protein modifications, and the increasing application of such technologies to the study of rheumatological diseases will further our understanding of autoantigenicity.
ISSN:1462-0324
1462-0332
DOI:10.1093/rheumatology/ken014