Molecular analysis of C3 allotypes in patients with systemic vasculitis

The third component of complement (C3) exists in two main allotypic forms, C3S and C3F, distinguished at the DNA level by a single base change. An increased frequency of the rarer C3F allele has been reported in patients with the autoantibody nephritic factor and in several other autoimmune conditions such as rheumatoid arthritis and IgA nephropathy. Studies of the immunogenetic factors predisposing to the development of systemic vasculitis have produced conflicting results and no major genetic predisposing factors have been identified. We have studied the C3S/F polymorphism in 63 patients with systemic vasculitis using DNA allotyping by the amplification refractory mutation system, a modification of the polymerase chain reaction. The allele frequency in these patients was C3S 0.71, C3F 0.29 (expected C3S 0.8, C3F 0.19; chi-squared=5.1, P<0.025), with the average relative risk for the development of systemic vasculitis associated with the presence of a C3F allele being 2.6. Moreover, there was a marked excess of C3FF homozygotes (11/63, [17.5%], versus 4% expected: chisquared=9.5, p