Decreased C5b67-inhibitor activity in two families with hereditary functional deficiency of the eighth component of complement.
In addition to its role in hemolysis and host defense against Neisseria infection, the eighth component of human complement (C8) is one of several plasma proteins that are C5b67-inhibitors (C5b67-INH). The recent identification in our laboratory of two new families with hereditary deficiency of C8 provided an opportunity to study further the role of C8 as a C5b67-INH. Based on mixing and reconstitution experiments, the deficiency of C8 seemed to be due to a selective lack of the C8 beta-chain in one family and the C8 alpha-gamma subunit in the other family. Sera from individuals homozygous for the C8 abnormality were substantially deficient in C5b67-INH activity as well as totally deficient in hemolytic activity. Sera from control individuals possessed approximately 2500 C5b67-INH U/ml, whereas sera from the C8-deficient individuals had markedly depressed C5b67-INH activity, with a mean of only 428 U/ml. C5b67-INH activity was completely reconstituted in C8-deficient serum by the addition of purified human C8. We conclude that C8 constitutes the substantial majority of the C5b67-INH activity of normal human serum.
D000293:Adolescent; D000368:Aged; D003185:Complement C8 / Q000172:deficiency* / Q000235:genetics; D003169:Complement Inactivator Proteins / Q000172:deficiency*; D003165:Complement System Proteins / Q000032:analysis; D006461:Hemolysis; D006801:Humans; D008297:Male; D008581:Meningitis / Q000235:genetics / Q000276:immunology; D010375:Pedigree
D003185:Complement C8; D003169:Complement Inactivator Proteins; D003165:Complement System Proteins