The recent appreciation that a subset of anti-DNA antibodies cross-reacts with the N-methyl-d-aspartate receptor encourages a renewed examination of antibrain reactivity in systemic lupus erythematosus (SLE) autoantibodies. Moreover, investigations of their autospecificity present a paradigm for studies of antibrain reactivity and show that (1) serum antibodies access brain tissue only after a compromise of blood-brain barrier integrity, (2) the same antibodies have differential effects on brain function depending on the region of brain exposed to the antibodies, and (3) insults to the blood-brain barrier are regional rather than diffuse. These studies suggest that an anatomic classification scheme for neuropsychiatric SLE may facilitate research on etiopathogenesis and the design of clinical trials.
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