Complement and the direct mediation of immune glomerular injury: A new perspective

Abstract

The importance of the complement system in mediating glomerular disease has been confirmed in recent studies. However, these studies implicate the C5b-9 portion of the complement system rather than neutrophil-mediated inflammation as a major effector mechanism. A direct functional effect of C5b-9 on glomerular permeability has now been clearly established in several models of both in situ immune complex nephritis and in anti-GBM nephritis. The presence of C5b-9 neoantigens in immune deposits and at other sites in a variety of human renal diseases suggests that this mechanism may be pathogenic in man as well. The molecular basis for this direct complement effect is unclear. Hemodynamic factors or lytic effects on glomerular cells or extracellular matrices cannot yet be excluded. However, non-lethal effects of C5b-9, activated by immune or non-immune mechanisms, on the metabolism of resident glomerular cells stimulating the release of mediators which damage the filtration barrier or altering the synthesis of capillary wall components seem more probable explanations for this new mechanism of glomerular injury.