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New insights into the functional role of the rheumatoid arthritis shared epitope
Author(s) -
de Almeida Denise E.,
Ling Song,
Holoshitz Joseph
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.2011.03.035
Subject(s) - autoimmunity , calreticulin , epitope , immunology , innate immune system , signal transduction , arthritis , immune system , biology , autoimmune disease , rheumatoid arthritis , receptor , nitric oxide , microbiology and biotechnology , antigen , genetics , antibody , endocrinology , endoplasmic reticulum
The shared epitope (SE) – an HLA‐DRB1 ‐encoded 5‐amino acid sequence motif carried by the vast majority of rheumatoid arthritis (RA) patients – is a risk factor for severe disease. The mechanistic basis of RA‐SE association is unknown. This group has previously demonstrated that the SE acts as a signal transduction ligand that activates nitric oxide and reactive oxygen species production. SE‐activated signaling depends on cell surface calreticulin, a known innate immunity receptor previously implicated in immune regulation, autoimmunity and angiogenesis. Recent evidence that the SE enhances the polarization of Th17 cells, which is a key mechanism in autoimmunity, is discussed highlighting one of several potential functional effects of the SE in RA.