Nervous System Lupus: Pathogenesis and Rationale for Therapy

Several different pathogenic mechanisms appear to be involved in CNS lupus. These include: B-cell/autoantibody-mediated nervous system compromise; immune complex deposition and vasculitis; microthrombosis and vasculopathy; aberrant MHC Class II antigen expression with T-cell mediated disease (multiple-sclerosis model); and, cytokine-induced brain inflammation. These processes are not mutually exclusive: there exist in vitro and in vivo models for each of these. A number of autoantibodies, especially those with specificities for shared neuronal/lymphocyte antigens, are associated with certain forms of cognitive dysfunction or overt nervous system manifestations. In MRL/lpr mice, lymphoid infiltrates in the brain parenchyma are related to a neurobehavioural dysfunction which develops very early in the course of autoimmune disease. Recent results, both in animal models and in human studies on the therapeutic effects of corticosteroids, immunosuppressive drugs or anticoagulants on clinical and subclinical manifestations of CNS lupus are highlighted in an attempt to develop a rationale for intervention based upon presumed pathogenesis.