SHARING OF MHC HAPLOTYPES AMONG PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS FROM UNRELATED CAUCASIAN MULTICASE FAMILIES - DISEASE ASSOCIATION WITH THE EXTENDED HAPLOTYPE [HLA-B8,SC01,DR17]

Objective. Systemic lupus erythematosus (SLE) is an autoimmune rheumat ic disease often clustered in families. We investigated the associatio n between MHC haplotypes and SLE in multicase Caucasian families. Meth ods. Ten consecutive families with 2 or more patients with SLE, in tot al 27 patients among 66 individuals, were studied. MHC haplotypes were determined by typing for HLA-A, B, C, DR, and DQ by serological and D NA methods. Complotypes were determined by protein typing and C4 gene polymorphism by DNA analysis. Results. Fifty-four independent MHC hapl otypes were found. Ten of the 31 haplotypes in the patients with SLE w ere examples of the extended haplotype [HLA-B8,SC01,DR17]. Six of thes e were found in 2 or more patients with SLE within the same family. Al l the 14 SLE sib-pairs in the families shared at least one haplotype a nd in 9 of the sib-pairs the shared haplotype was [HLA-B8,SC01,DR17]. Three SLE associated haplotypes were [HLA-B7,SC31,DR15]. Four of the 2 7 patients with SLE were C4A deficient. Two C2 deficient siblings were homozygous for the haplotype [HLA-B18,S042,DR15]. Conclusion. We demo nstrate that a very limited number of MHC haplotypes are associated wi th familial SLE. The haplotype [HLA-B8,SC01,DR17] was closely related with the disease. There was no evidence suggesting familial SLE consti tutes a disease subset. Determination of MHC haplotypes in multicase f amilies is of value for assessment of disease susceptibility.