Is immunogenetic susceptibility to neuropsychiatric systemic lupus erythematosus (SLE) different from non-neuropsychiatric SLE?

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.