Complement phenotypes in glomerulonephritis: increased frequency of homozygous null C4 phenotypes in IgA nephropathy and Henoch-Schönlein purpura.

Polymorphism of three complement genes (C4A, C4B, and BF) located within the major histocompatibility complex was studied in 48 biopsy-proven IgA nephropathy patients and nineteen patients with Henoch-Schönlein purpura (HSP). Polymorphism was determined by immunoelectrophoretic techniques and functional activity using an overlay of sheep cells in agarose and C4 deficient sera. The subjects were divided into four large groups according to the presence or absence of a C4 null allele (a gene producing no identifiable gene product): group 1 (no null variants), group 2 (one C4A null variant), group 3 (one C4B null variant), and group 4 (two null variants at either the C4A or C4B locus, that is, homozygous null). Patients had a significantly increased frequency of group 4 phenotypes (homozygous null): (12 of 67 patients, 17.8%) as compared to controls (4 of 102 patients, 3.9%, P = 0.0031). Both IgA (P = 0.045) and HSP patients (P = 0.003) had a greater frequency of a C4 homozygous null phenotype. The serum C4 concentration was higher in patients than in controls (740 mg/ml and 576 micrograms/ml, respectively, P = less than 0.001) whether evaluated together or by C4 phenotypic group. The association between the presence of IgA nephropathy or HSP with a homozygous C4 null phenotype is of unknown significance but suggests a predisposition to development of HSP or IgA nephropathy for individuals with the C4 homozygous null phenotype.