Inhibition of terminal complement: a novel therapeutic approach for the treatment of systemic lupus erythematosus

The importance of the complement system in the pathophysiology of systemic lupus erythematosus (SLE) is clear although individual complement components play very different roles in the disease process. Early complement proteins are critical in the clearance of immune complexes and apoptotic bodies, and their absence predisposes individuals to SLE. Conversely, activation of terminal complement is associated with exacerbations of disease and damage to tissues and organs, particularly in lupus nephritis. Monoclonal antibodies that specifically inhibit terminal complement activation while preserving the critical functions of the early complement cascade have now been developed. These antibodies target the C5 complement protein, blocking its cleavage and the subsequent generation of potent proinflammatory molecules. Anti-C5 therapeutics have recently been investigated in an animal model of SLE and in a Phase I single dose study in humans. The results of these studies and the multiple roles of complement in SLE are discussed.