Neuropathological features of a lupus-like disorder in autoimmune mice

Neurological syndromes are prominent in systemic lupus erythematosus, but the neuropathological and mechanisms resulting in neurological dysfunction are unknown. We report a neuropathological study of the central nervous system in female NZB/W F1 mice, an animal model of systemic lupus erythematous. NZB/W mice were studied at 3, 5, 8, 12, and 14 months of age, and 36-month-old female C57B16N/NIA mice were studied as aged controls. A lymphoproliferative process was identified in the central nervous system of 39% of 8- to 12-month-old and all 14-month-old NZB/W mice. Infiltrates of lymphocytes and plasma cells were seen in subarachnoid, choroid plexus interstitial, and Virchow-Robin spaces. Lymphoid cells occasionally infiltrated brain parenchyma or accumulated as nodular masses. Concomitant visceral lymphoid infiltration was noted in 14-month-old mice. Dense deposits were seen ultrastructurally in the basal lamina of brain parenchymal capillaries of 14-month-old NZB/W mice. These dense deposits were similar in appearance to immune complexes described in glomerular basal lamina, and appeared concomitantly with an advanced lupus-like glomerulopathy. Similar deposits were not observed in choroid plexus. The possible relevance of these neuropathological changes to human central nervous system lupus is discussed.