OBJECTIVES: To analyse frequency of HLA class II antigens (DR and DQ) and lymphocytotoxic autoantibodies in patients with systemic lupus erythematosus (SLE) and subsets with or without neuropsychiatric involvement. METHODS: Ninety three patients with SLE (42 with neuropsychiatric features) were typed for HLA class II antigens and investigated for the presence of lymphocytotoxic autoantibodies by a complement dependent microlymphocytotoxicity assay. A total of 191 controls of similar ethnic background were also typed for HLA antigens. RESULTS: HLA-DR3 antigen was increased in the total group of patients with SLE (p = 0.003) and in the neuropsychiatric group (p = 0.002). HLA-DR4 antigen frequency was increased in non-neuropsychiatric patients (p = 0.001) and decreased in patients with neuropsychiatric SLE (p = 0.0005). Comparisons of HLA frequencies between subgroups of patients showed decreased HLA-DR4 (p < 0.0001) and increased HLA-DR9 and HLA-DQ2 antigens (p = 0.0008 and 0.005 respectively) in the neuropsychiatric group. The frequency of lymphocytotoxic autoantibodies was increased in neuropsychiatric patients with SLE having HLA-DR9 specificity (p = 0.04). CONCLUSION: HLA-DR4 may have a protective specificity for the development of neuropsychiatric features of SLE and HLA-DR9, in addition to HLA-DR3, and the presence of lymphocytotoxic auto-antibodies may predispose to neuropsychiatric abnormalities.
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