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Autoantibody depletion ameliorates disease in murine experimental autoimmune encephalomyelitis

Challa, DK;Bussmeyer, U;Khan, T;Montoyo, HP;Bansal, P;Ober, RJ;Ward, ES;

Much data support a role for central nervous system antigen-specific antibodies in the pathogenesis of multiple sclerosis (MS). The effects of inducing a decrease in (auto)antibody levels on MS or experimental autoimmune encephalomyelitis (EAE) through specific blockade of FcRn, however, remain unexplored. We recently developed engineered antibodies that lower endogenous IgG levels by competing for binding to FcRn. These Abdegs (antibodies that enhance IgG degradation) can be used to directly assess the effect of decreased antibody levels in inflammatory diseases. In the current study, we show that Abdeg delivery ameliorates disease in an EAE model that is antibody dependent. Abdegs could therefore have promise as therapeutic agents for MS.