Five conditions in which the
alternative pathway C3 convertase, C3b,Bb, circulates in excess as a result of
factor H dysfunction are frequently accompanied by
nephritis. These convertase-related
nephritides are seen in association with heterozygous absence of a binding site for
factor H on C3b (Marder disease), homozygous
factor H deficiency, circulating
factor H inhibitor, and with the nephritic factors, one of the amplification loop and the other of the terminal pathway, found in
membranoproliferative glomerulonephritis (MPGN) types II and III, respectively. Observations which relate convertase to glomerular deposits are: (1) in
MPGN type II, subepithelial deposits on the paramesangial segments of the glomerular basement membrane are with high frequency present in patients hypocomplementemic at biopsy, but not in those normocomplementemic; (2) in MPGN type III paramesangial deposits are similarly found with hypocomplementemia but are present for up to 1 year after normocomplementemia is achieved; (3) in MPGN type III, subendothelial deposits are present only with hypocomplementemia. The principal deposits found in
factor H deficiency and in Marder disease are also paramesangial. Differences in the incidence, severity, and morphology of the
nephritides accompanying convertase in excess may relate to the characteristics of the circulating convertase and/or to the C3 conversion products formed by it.