Therapeutic treatment with PD-1 agonist antibody prevents progressive autoantibody increase in murine autoimmune disease models 2258756

Abstract

Abstract Introduction Autoimmune diseases are chronic inflammatory conditions with no complete cure. Repeated inflammatory episodes against self-antigens gradually accumulates tissue damage leading to morbidities; therefore, the treatment focuses on the management of disease to reduce the frequency and severity of inflammatory episodes. We have identified PD-1 agonist antibodies that can stimulate the immunosuppressive activity of PD-1. PD-1 agonist antibodies could suppress not only effector functions of activated T cells but also antibody development by targeting Tfh cells. The current study is designed to elucidate the efficacy of PD-1 agonists against autoimmune tissue damage by effector cells and autoantibody. Methods The therapeutic efficacy of PD-1 agonist antibody was tested using two autoimmune disease models: chronic graft-versus-host disease and MRL/lpr mice. Chronic graft-versus-host disease was induced in BDF1 mice by the transfer of CD8+-depleted splenocytes from human PD-1-knock-in B6 mice. Human PD-1-knock-in MRL/lpr mice received PD-1 agonist antibody treatment starting at 8 weeks old. Results Chronic graft-versus-host disease is a lupus model where single transfer of allogenic cells sufficiently induced anti-dsDNA antibody production. Treatment after the disease onset with PD-1 agonist antibody prevented further autoantibody increase by the additional transfer of B6 cells. The increase of autoantibody is far more progressive in MRL/lpr mice, but PD-1 agonist antibody starting blocked the increase of autoantibodies as well as splenomegaly for an extended time. Conclusion PD-1 agonists has a potential to be a novel therapeutic approach for the management of autoimmune diseases to keep them under control. Funding Source n/a Topic Categories Therapeutic Approaches to Autoimmunity (THER)