Serum concentrations of C4 isotypes and factor B in type I C2 deficiency suggest haplotype-dependent quantitative expression of MHC class III complement genes

The complement protein C4 exists as two isotypes, C4A and C4B, encoded by genes in the major histocompatibility complex (MHC) class III region. The serum concentrations of C4A4 were lower than those of C4B2 in serum from 19 individuals homozygous for type I C2 deficiency (p < 0.0002). These individuals all had the S042 complotype and most of them were homozygous for the haplotype HLA-B18,S042,DR2. In 14 individuals heterozygous for the C2Q0 gene and with the C4A4, C4B2 phenotype and in 51 individuals with the C4A3, C4B1 phenotype, the isotype concentrations were equal. Factor B concentrations in the C2-deficient individuals were lower than those in individuals with the C4A3, C4B1 phenotype (p < 0.0001). The findings strongly suggest that the quantitative expression of C4 isotypes and factor B is MHC haplotype dependent. C4 null alleles cannot be accurately determined by measuring relative C4 isotype serum concentrations.