Targeting B lymphocyte stimulator in systemic lupus erythematosus and other autoimmune rheumatic disorders.

B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression of BLyS in mice can lead to systemic lupus erythematosus (SLE)-like disease and to Sjögren's syndrome (SS)-like disease. Treatment of mice with established SLE with BLyS antagonists 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 SLE, rheumatoid arthritis or SS. Results from a Phase I clinical trial with a BLyS antagonist in human SLE have shown the antagonist to be biologically active and safe. These features collectively point to BLyS as an attractive therapeutic target in human disease.