A strong association between null alleles at the C4A locus in the major histocompatibility complex and systemic sclerosis.

Allotyping of the major histocompatibility complex (MHC)-linked complement component C4 has revealed a strong association of the null allele, C4AQ0, with systemic sclerosis (SSc). Sixty-four percent of patients with SSc carried the C4AQ0 allele, compared with 17% of the control group. Twenty-five patients and their families were typed for HLA antigens (A, B, Cw, and DR) and the MHC-linked complement components C4 and factor B to identify haplotypes in the MHC linkage group and C4 null alleles. Strong allelic association of HLA-B8 and DR3 with C4AQ0 probably explains the previously reported association of SSc with the extended haplotype carrying HLA-B8 and DR3. Ninety-two percent of the patients had either C4AQ0 or DR5; 31% of the controls had either C4A*Q0 or DR5.