Neuropsychiatric lupus and association with cerebrospinal fluid immunoglobulins: a pilot study.

BACKGROUND: Recent experimental evidence points to brain-reactive antibodies as a key factor in the pathogenesis of neuropsychiatric systemic lupus erythematosus (central nervous system-SLE). However, clinical studies in which circulating (serum) autoantibodies were correlated with neuropsychiatric manifestations have not produced consistent findings. OBJECTIVES: To test the hypothesis that autoantibodies in cerebrospinal fluid are more reflective of functional brain damage. METHODS: We compared the behavioral profiles of 12 NP-SLE patients, some of whom had immunoglobulin G in their CSF. RESULTS: Western blotting revealed heavy and light chain IgG bands in six patients similar in age to the subgroup of CSF IgG-free patients. A series of serological measures did not differ between the subgroups, but SLEDAI scores and daily steroid doses were higher in patients with IgG in their CSF. All three patients with severe deficits in verbal and executive functions were positive for the CSF IgG, while three other patients with psychosis were CSF IgG-negative. CONCLUSIONS: Although the present sample size is relatively small, the results support the relationship between disease severity and central manifestations of autoimmunity. They also emphasize the importance of clinical studies that compare subpopulations of NP-SLE patients and justify development of animal models in which controlled immune mechanisms induce specific deficits in behavior.