NERVOUS-SYSTEM LUPUS - PATHOGENESIS AND RATIONALE FOR THERAPY

Several different pathogenic mechanisms appear to be involved in CNS l upus. These include: B-cell/autoantibody-mediated nervous system compr omise; immune complex deposition and vasculitis; microthrombosis and v asculopathy; aberrant MHC Class II antigen expression with T-cell medi ated disease (multiple-sclerosis model); and, cytokine-induced brain i nflammation. These processes are not mutually exclusive: there exist i n vitro and in vivo models for each of these. A number of autoantibodi es, 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 infi ltrates in the brain parenchyma are related to a neurobehavioural dysf unction which develops very early in the course of autoimmune disease. Recent results, both in animal models and in human studies on the the rapeutic effects of corticosteroids, immunosuppressive drugs or antico agulants on clinical and subclinical manifestations of CNS lupus are h ighlighted in an attempt to develop a rationale for intervention based upon presumed pathogenesis.