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Citrullination of autoantigens: Upstream of TNFα in the pathogenesis of rheumatoid arthritis
Author(s) -
Quirke Anne-Marie,
Fisher Benjamin A.C.,
Kinloch Andrew J.,
Venables Patrick J.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.06.006
Subject(s) - citrullination , rheumatoid arthritis , pathogenesis , immunology , medicine , tumor necrosis factor alpha , upstream (networking) , citrulline , biology , genetics , computer science , amino acid , arginine , computer network
The discovery of autoimmunity to citrullinated protein/peptide antigens (ACPA) has led the concept that ACPA may be the essential link between disease susceptibility factors and the production of TNFα, which ultimately accounts for the disease phenotype. In this review we will consider (1) the mechanisms of citrullination, both physiological and pathological, (2) how known genetic and environmental factors could drive this peculiar form of autoimmunity and (3) how the immune response could lead to excessive production of TNFα by the synovial cells and ultimately to the disease phenotype (Fig. 1).