This study evaluates spontaneously occurring antineuronal antibodies in an autoimmune mouse model of systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is a multisystem disease characterized by the spontaneous production of multiple autoantibodies. Neurologic abnormalities are common in SLE but the pathogeneses are not well understood. Despite evidence that antibodies reactive with neuronal tissue are present in the serum and cerebrospinal fluid of patients with CNS-SLE, the long course of the disease and lack of access to central nervous system tissue makes human investigation difficult. (NZBxW)F1 hybrid mice spontaneously develop polyclonal B cell hyperactivity with formation of many autoantibodies including anti-DNA antibodies. Circulating immune complexes occur and immune complex deposition in the choroid plexus is described. In order to ascribe a role for antibodies in the pathogenesis of central nervous system disease, the following criteria should be met: 1. determine whether antibodies reactive with neurons exist, 2. demonstrate access of antibodies to CNS, 3. describe effects of antibody on in vitro neuronal function, 4. determine if antibody can produce dysfunction in vivo. In my preliminary studies antineuronal antibodies have been identified in the serum by indirect immunofluorescence against frozen brain slices and cultured neuroblastoma cells and by an ELISA assay using primary brain cultures. Documenting that these antibodies are present within the CNS is being pursued by immunoelectrophoresis of bound and unbound proteins from brain slices. The relevance of these antibodies will depend on whether or not they affect neuronal function. In order to study the antineuronal antibodies in more detail: 1. monoclonal antibodies will be made and selected for reactivity on primary brain cultures, 2. experiments are planned to determine the localization of binding of monoclonal antibody to specific cell populations within the CNS (antigenic specificity is also being studied by immunoblot and immunoprecipitation techniques), 3. in vitro effects on neuronal function will be investigated in terms of effect of antibody on a. spontaneous activity, b. repetitive firing of transcellular recordings of cultured neurons and c. resting membrane potential. 4. in vivo studies are planned in which labeled monoclonal antibodies will be administered to mice.
