Targeting BLyS in rheumatic disease: the sometimes-bumpy road from bench to bedside.

Abstract

BLyS family ligands and receptors are key players in the selection and survival of most mature B lymphocytes. The fundamental role of BLyS in transitional B cell selection, coupled with the relative BLyS-independence of memory B cells and plasma cells, suggests that BLyS may be a useful therapeutic target in strategies directed against preimmune B cell pools. Several agents that target BLyS are in clinical trials now, and we summarize recent results here, with a focus on systemic lupus erythematosus (SLE). Belimumab, a human neutralizing anti-BLyS monoclonal antibody, has delivered moderate but positive results in two separate phase III clinical trials for SLE, and was recently recommended for approval by an FDA advisory panel. Additional agents targeting BLyS or other members of this cytokine receptor family are also being tested in clinical trials. Together, these trials should yield novel therapies for a debilitating and often intractable illness and offer insights that in turn should foster subsequent generations of personalized, targeted therapies for rheumatic diseases.