Complement and glomerulonephritis: new insights

Abstract

The last few years have seen a huge increase in our understanding of the role of the complement system and its regulation in glomerular disease. Our aim is to summarize the most important advances in this field. The role of complement in systemic lupus erythematosus continues to be elucidated. Classical pathway components protect from the development of autoimmunity, at least in part, through their role in the clearance of apoptotic cells. In contrast, the alternative pathway plays a direct role in exacerbating glomerular injury. Anti-C1q antibodies are related to activity in lupus nephritis and recent studies have shown that they are directly pathogenic in animal models. Proteinuria, whatever the cause, may lead to tubulointerstitial injury and complement activation adds to this process. In particular, deposition of terminal components of complement in the tubular lumen contributes to interstitial myofibroblast activation. There is increasing evidence for the role of complement regulatory proteins in glomerular injury. In particular, abnormalities of factor H or of CD46 may predispose to atypical haemolytic uraemic syndrome. The control proteins also protect against injury in immune complex glomerulonephritis. Advances in our understanding of the role of complement in glomerular injury point to the likely therapeutic benefits of targeting the complement system. Many new drugs are becoming available. Careful dissection of the pro and antiinflammatory effects of the complement system which the experimental models allow will assist in designing directed therapy that will avoid the detrimental effects of nonspecific systemic complement inhibition.