Familial systemic lupus erythematosus: the role of genetic and environmental factors

OBJECTIVE: To examine the contribution of genetic and environmental factors to disease occurrence in 26 families with two or more members affected with systemic lupus erythematosus (SLE). METHODS: Genetic and environmental factors were examined by HLA-A, B, C/DR typing and by determining the presence of lymphocytotoxic antibodies (LCA) in patients and their consanguineous and non-consanguineous relatives. RESULTS: No association between SLE and HLA-A, B, C antigens was found. There was, however, a significant association with HLA-DR2 in white subjects with SLE. The most striking finding was that HLA sharing was increased among the affected members, suggesting genetic similarities. Seven of 14 sib pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. Another interesting finding was that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies. CONCLUSION: Genetic factors have a role in the development and expression of SLE. Environmental factors may trigger the disease in genetically susceptible hosts.