Nephritic factors predispose to chronic glomerulonephritis.
Chronic glomerulonephritis has been reported in three rare conditions in which factor H of the complement system does not function normally. Factor H is essential for the inactivation of the C3b-dependent convertase, C3b,Bb, which is constantly being formed in vivo. With factor H dysfunction, this convertase accumulates and produces hypocomplementemia. Twenty-two individuals have been reported with the three forms of H dysfunction, and 12 have displayed evidence of chronic glomerulonephritis. In addition, matings of certain Yorkshire pigs result in offspring that are homozygous deficient in factor H and have a high incidence of a severe hypocomplementemic glomerulonephritis closely resembling membranoproliferative glomerulonephritis type II. The hypothesis proposed is that the nephritis that develops with these forms of H dysfunction is in some way the result of circulating convertase. The corollary is that nephritic factors, also producing H dysfunction and higher than normal circulating levels of the C3b-dependent convertase, are responsible for the glomerulonephritides with which they are associated, mainly membranoproliferative glomerulonephritis types II and III. Nephritic factors are autoantibodies that bind to the C3b-dependent convertase and render it resistant to dissociation by factor H. Although nephritic factors are currently considered epiphenomena, their role in the pathogenesis of membranoproliferative glomerulonephritis should be reconsidered based on the evidence that circulating convertase is nephritogenic.
West
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Children's Hospital Research Foundation, Children's Hospital Medical Center, Cincinnati, OH 45229.
D001323:Autoantibodies / Q000276:immunology*; D002908:Chronic Disease; D003176:Complement C3 / Q000172:deficiency; D050577:Complement C3-C5 Convertases / Q000276:immunology; D011415:Complement Factor B / Q000172:deficiency; D017242:Complement Factor H / Q000172:deficiency*; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*
D001323:Autoantibodies; C493495:CFH protein, human; D003176:Complement C3; D007074:Immunoglobulin G; D017242:Complement Factor H; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B