An inherited defect in the C3 convertase, C3b,Bb, associated with glomerulonephritis.
The control of the amplification C3 convertase, C3b,Bb, of the serum complement system has been found to be defective in five members of a family spanning three generations. One of the five has membranoproliferative glomerulonephritis (MPGN) type III and another has mild idiopathic rapidly progressive glomerulonephritis. The defect is manifested by low serum concentrations of C3 and usually factor B with normal levels of the proteins which control the convertase, H and I. C3 nephritic factor (C3NeF) was not demonstrable. Enhanced C3 conversion was produced by the incubation of their serum at 37 degrees C for 30 min. This conversion was further accelerated by incubation after increasing the serum magnesium concentration by increments ranging from 0.25 to 1.9 mM. Incremental additions of H to serum depleted of H indicated that the amplification convertase of affected family members required more H for its inhibition than did that of normal subjects. This requirement was reduced by the addition of purified normal C3 but not by the addition of purified C3 of the propositus. It is postulated that affected family members are heterozygous for a gene producing an abnormal C3 which, as a constituent of the amplification convertase, C3b,Bb, confers resistance to H. Investigation of this apparently nephritogenic defect may provide insight into the pathogenesis of these glomerulonephritides.
D000328:Adult; D002648:Child; D003166:Complement Activating Enzymes / Q000235:genetics*; D003176:Complement C3 / Q000172:deficiency; D003178:Complement C3 Nephritic Factor / Q000172:deficiency; D050577:Complement C3-C5 Convertases / Q000235:genetics*; D003179:Complement C3b / Q000235:genetics; D011415:Complement Factor B / Q000172:deficiency; D005260:Female; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D010375:Pedigree
D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D003179:Complement C3b; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B