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Immmunopathogenesis of Rheumatoid Arthritis
Author(s) -
Hoffmann Markus,
Hayer Silvia,
Steiner Guenter
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04753.x
Subject(s) - rheumatoid arthritis , immunology , autoantibody , heterogeneous nuclear ribonucleoprotein , proinflammatory cytokine , arthritis , rheumatoid factor , tumor necrosis factor alpha , medicine , autoimmunity , antigen , antibody , ribonucleoprotein , inflammation , biology , rna , biochemistry , gene
Rheumatoid arthritis (RA) is a severe autoimmune disorder of unknown etiology. Major autoantigens include immunoglobulin G (which is targeted by rheumatoid factor), citrullinated proteins, and the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. To obtain more insight into the pathogenic role of arthritogenic autoantigens, we studied autoimmune responses in two animal models of RA, which are independent of immunization with exogenous antigens, namely human tumor necrosis factor‐α (TNF‐α)‐transgenic (hTNFtg) mice and rats with pristane‐induced arthritis (PIA). Serologic and cellular studies revealed autoantibodies to hnRNP‐A2 in these animals and pronounced T‐cell reactivity to hnRNP‐A2 and the presence of rheumatoid factor in PIA, while citrullinated antigens were not targeted. Furthermore, hnRNP‐A2 was found to be highly overexpressed in the joints of mice and rats affected by arthritis. Thus, unspecific proinflammatory stimuli, such as TNF‐α or pristane, may induce pathogenic autoimmune reactions that may drive an inflammatory process, leading to the development of erosive arthritis.