Therapeutic targeting of B lymphocyte stimulator (BLyS) in the rheumatic diseases.

B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression of BLyS in mice can lead to clinical and serological features of systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Treatment with BLyS antagonists of mice with established SLE ameliorates disease progression and enhances survival. Moreover, similar treatment of mice with inflammatory arthritis ameliorates the ongoing inflammation and subsequent joint destruction. In humans, BLyS overexpression is common in patients with several rheumatic diseases, including SLE, rheumatoid arthritis (RA), Sjögren's syndrome, scleroderma, Wegener's granulomatosis, and ANCA-associated vasculitis. Results from phase-II clinical trials with a BLyS antagonist in human SLE and RA have shown the antagonist to have biological and clinical activity along with a favorable safety profile. These features collectively point to BLyS as an attractive therapeutic target in human rheumatic diseases.