Targeting BAFF in autoimmunity

BAFF and APRIL are TNF-like cytokines that support survival and differentiation of B cells. The early appreciation that overexpression of BAFF leads to B cell expansion and a lupus-like syndrome in mice, and the demonstration that BAFF inhibition delays lupus onset in spontaneous mouse models of SLE and other autoimmune diseases has rapidly led to the development of strategies for inhibiting both BAFF and APRIL. The commercialization of this new class of drugs has proceeded in parallel with the continuing elucidation of the biology of the cytokines and their receptors. Recent studies have uncovered a role for BAFF in enhancing both innate and adaptive immune responses and in amplifying aberrant pathways that arise during inflammation. Two phase III studies of an anti-BAFF antibody have yielded positive, although modest, results in SLE and alternate inhibitors are being tested in a variety of autoimmune diseases in which BAFF may play a pathogenic role.