Rationale for CD40 pathway blockade in autoimmune rheumatic disorders

CD40 and its ligand CD40L (CD154) belong to the tumor necrosis factor receptor superfamily and are expressed by a variety of immune and non-immune cells. CD40L plays a central role in co-stimulation and regulation of the immune response via activation of cells expressing CD40. Imbalance of the CD40–CD40L co-stimulatory pathway has been reported in many autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome, thus supporting its role in the breach of immune tolerance that is typical of these diseases. Targeting CD40–CD40L signalling might represent a novel therapeutic option for several autoimmune disorders.