Hereditary C6 deficiency in man

Abstract

An 18-year-old black female (D.B.) in good general health was found to have no hemolytic activity in serum CH50 titrations. Functional assays yielded normal values for all C components except C6. C6 was not detectable in plasma or serum by two different functional assays nor by antigenic analysis using monospecific anti-C6 antibody. Hemolytic activity was restored by addition of functionally pure C6. By specific functional assay, both parents and 5 of 6 available sibs had approximately half-normal serum C6 levels and 1 sib was normal. Biologic properties of D.B. serum include: a) absent bactericidal activity against S. typhi 0 901 with or without added rabbit antibody; b) normal generation of chemotactic activity for human neutrophils in the presence of endotoxin or aggregated IgG; c) ability to sensitize appropriate cells for immune adherence of agglutination by anti-C3 Coombs serum; and d) inability to lyse PNH red cells in either acid hemolysis or "sugar water" tests. An extensive clotting workup by standard methods was within normal limits. These studies document for the first time a human kindred with C6 deficiency. This defect exhibits a classic mendelian autosomal inheritance, with all 3 genotypes being recognizable. Unlike the C6-deficient rabbits studied by others, the homozygous C6-deficient human exhibits chemotactic and coagulation functions within the range of normal.