Immune Profiling of Encephalitis

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PROJECT SUMMARY Encephalitis is an inflammatory disease of the brain caused by infection or autoimmune conditions. The most common type of autoimmune encephalitis (AE) is associated with high titers of antibodies against N-methyl-D- aspartate type glutamate receptors (NMDARs), termed αNMDAR-AE. Anti-NMDAR antibodies bind, cross-link, and internalize NMDAR receptors leading to altered neuronal function. Removal of anti-NMDAR antibodies has thus been the focus of first-line therapy, but recurrent attacks occur even in treated patients. Anti-NMDAR antibodies are produced by antibody secreting cells (ASCs), which arise from the memory B cell pool. We hypothesize that memory B cells and ASCs of αNMDAR-AE patients express antibodies that bind to NMDARs. Establishing that the memory B cell pool of αNMDAR-AE patients harbors a high frequency of NMDAR-reactive memory B cells would be the first step towards understanding the immunopathogenesis of αNMDAR-AE, and may prompt consideration of additive therapies that would effectively remove NMDAR- reactive memory B cells early in the treatment and management of αNMDAR-AE patients.