What causes rheumatoid nodules?

The pathogenesis is not understood, but the evidence suggests that rheumatoid arthritis occurs in genetically susceptible patients after an arthritogenic microbial antigen exposure. The identity of the microbial trigger has not been established, although considerable attention has been placed on the Epstein-Barr virus. Once the process is initiated, a complex autoimmune disease develops characterized by increased numbers of CD41 T cells in the joint, which also activate B cells that produce autoantibodies (primarily IgM) to the Fc portion of autologous IgG. The antigen that provokes the autoimmune response has not been fully established, but research is focusing on type 2 collagen, human cartilage glycoprotein-39, human stress protein BiP, and several different heat shock proteins. How this autoimmune response produces rheumatoid nodules is not clear.


Bodman-Smith MD, Corrigall VM, Berglin E, et al: Antibody response to the human stress protein BiP in rheumatoid arthritis, Rheumatology (Oxford) 43:1283–1287, 2004.

Sawada S, Takei M: Epstein-Barr virus etiology in rheumatoid synovitis, Autoimmune Rev 4:106–110, 2005.