The alternative pathway C3 convertase and glomerular deposits.
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.
West
C D
CD
Division of Nephrology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
McAdams
A J
AJ
D003178:Complement C3 Nephritic Factor / Q000502:physiology; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D017242:Complement Factor H / Q000172:deficiency; D015432:Glomerulonephritis, Membranoproliferative / Q000201:enzymology*; D006801:Humans
C493495:CFH protein, human; D003178:Complement C3 Nephritic Factor; D017242:Complement Factor H; D050577:Complement C3-C5 Convertases