Is rheumatoid arthritis a B-cell haematological disease with a predilection for the joints? Following the B cell thread to its logical conclusion.

B-cell depleting therapy (BCDT) is effective in suppressing synovitis and erosions in rheumatoid arthritis suggesting that a cell of the B-lymphocyte lineage is critical in the pathogenesis of this disease. Non-Hodgkins lymphoma (NHL) also responds to BCDT but multiple myeloma (MM), does not as cells have differentiated beyond the CD20-bearing stage. However, there are similarities between B-NHL, MM and RA that suggest all 3 conditions could be initiated and perpetuated by the same cellular players. Numerous plasma cells and B cells are present within rheumatoid synovial membrane, and subarticular bone where they contribute to osteitis. On MRI scans this appears as bone oedema, which has been demonstrated to precede the development of bone erosions. Plasma cell clonality has been detected within RA synovial membrane and bone marrow. It is proposed that RA could represent a "forme fruste" of a B cell neoplastic condition, with production of autoantibodies that target a self-antigen within the joint. The activation of rheumatoid bone osteoclasts by anticitrullinated protein antibodies supports this theory. The erosions of RA would have parallels with the lytic lesions of MM but autoantigen targeting dictates that erosions occur at joint margins. This theory is discussed from rheumatologic and haematologic perspectives.