BAFF: B cell survival factor and emerging therapeutic target for autoimmune disorders

The prevailing treatment strategies for autoimmune disorders employ global immunosuppressants that have harmful side effects with long-term use. A new vision for drug development relies on the generation of therapeutics that have specific and narrow targets, such as pathogenic cell populations. The cellular processes that initiate and maintain B cell dysregulation are not well understood and autoimmune disease results, in part, from the survival and activation of self-reactive B cells. Such B cells produce tissue-damaging pathogenic autoantibodies. BAFF (B cell-activating factor belonging to the TNF family), a member of the TNF family of ligands, may play a role in B cell-mediated diseases. BAFF is a survival factor for peripheral B cells. When BAFF is overexpressed in mice, B cell number and immunoglobulin production is increased and an autoimmune-like phenotype is observed. Mouse models of lupus-nephritis have been shown to exhibit increased serum BAFF levels correlating with disease severity, and many autoimmune patients were found to have higher levels of circulating BAFF than healthy volunteers. Thus, modulating the level and activity of BAFF in these patients may alleviate symptoms associated with their disease. Several potential therapeutic inhibitors targeting BAFF are under investigation, including an anti-BAFF antibody and receptor-Fc fusion proteins.