Major histocompatibility complex extended haplotypes in systemic lupus erythematosus.

In a study of 32 white patients with systemic lupus erythematosus from 28 families, 60 unique chromosome 6 haplotypes were defined. The MHC extended haplotype HLA-B8, -DR3, SC01, GL02 was strongly disease-associated (0.09 patients, 0.02 controls, RR = 4.5, C.I. = 1.6-12.4, P less than 0.05), while the corresponding haplotype with the GL01 specificity was not increased in frequency (0.05 in both patients and controls). In the present data, the increase in the haplotype bearing GL02 accounted entirely for the association between HLA-DR3 and SLE. Furthermore, the phenotype of complete C4A deficiency was also strongly disease-associated (patients 0.14, controls 0.02, RR = 8.5, C.I. = 1.8-37.0, P less than 0.05). The only other MHC association in these patients was an increased occurrence of the HLA-B17, -DR7, SC61 haplotype (patients 0.07, controls 0.01, RR = 6.0, C.I. = 1.8-20.6, P corr. less than 0.05). The relationship between MHC markers and autoimmune disease appears to be a result of an association with MHC extended haplotypes and complete complement component deficiencies rather than with individual alleles. It is important that future studies include family members so that such haplotypes can be defined.