BRAIN-REACTIVE AUTOANTIBODIES AND COGNITIVE IMPAIRMENT IN SYSTEMIC LUPUS-ERYTHEMATOSUS

Nervous system involvement in SLE encompasses a wide array of clinical manifestations which may reflect multiple etiologic factors including autoantibodies to nervous tissue antigens. The aim of the present stu dy was to examine the association between autoantibodies to a wide ran ge of brain antigens and cognitive abnormalities in ani unselected pop ulation of 70 SLE patients. Using a battery of standardized neuropsych ological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared with 1/25 (4%) patients with rheumatoid arthritis a nd 1/23 (4%) healthy subjects (P = 0.04). Integral membrane proteins w ere isolated from dissociated brain cells by temperature-induced phase separation with Triton X-114. Synaptosomes were isolated by different ial centrifugation and membrane enriched tractions were prepared by le ctin affinity chromatography. Western blotting identified IgG reactivi ty to a wide range of proteins (MW 22-52 K) in SLE patients. The prote ins identified were distinct from well-characterized intracellular ant igens including ribosomal P proteins. There was no significant differe nce in the prevalence of anti-brain antibodies between SLE patients wh o were cognitively impaired and those who were not impaired. Furthermo re, there was no association between the presence of autoantibodies an d subsets of cognitive dysfunction. These results suggest that circula ting autoantibodies to brain antigens are not responsible for the abno rmalities in cognitive function in SLE patients.