BLyS or BAFF in Lupus and Other Autoimmune Diseases

B lymphocyte stimulator (BLyS), or B cell activating factor (BAFF), has been associated with a wide range of B-cell mediated autoimmune diseases, including lupus, lupus nephritis, rheumatoid arthritis, multiple sclerosis, Sjögren’s Syndrome, Graves’ Disease and others. BLyS, or BAFF, is a critical survival factor for B cells, and is required for B cell development and maintenance. Its involvement in B cell survival has been demonstrated in animal studies (Kalled 2005) and in human (Avery 2003) in vitro studies. BAFF is primarily expressed by macrophages, monocytes, and dendritic cells; BAFF receptor (BAFF-R) is expressed primarily on peripheral B cells. BAFF is specifically up-regulated in human and animal models of autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjögren’s syndrome, and rheumatoid arthritis (Gross 2000; Cheema 2001; Zhang 2001; Groom 2002; Kawasaki 2002). These finding suggests that high levels of BAFF may cause excessive survival signals to auto-reactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. Inhibition of BAFF is expected to block stages of B cell maturation, and subsequent antibody formation. Through this pathway, a BAFF antagonist could potentially modulate a variety of inflammatory and autoimmune conditions.

Although the cause of lupus is still not completely understood, B-cell activation and auto-antibody production are known to be central to the process. Evidence has emerged that over-expression of BLyS plays an important role in this disease process. In preclinical studies, transgenic mice created to over-express BLyS begin to exhibit symptoms similar to lupus. In addition, treatment of these same mice with BLyS antagonists appears to ameliorate the disease.