Targeting B Cells and Plasma Cells in Glomerular Disease.

Abstract: Loss of tolerance and the production of self-reactive autoantibodies by the humoral immune system are central to the pathogenesis of many glomerular diseases. These antibodies are produced by plasmablasts and plasma cells, the end-products of B cell lineage development within the bone marrow and secondary lymphoid tissues. In addition to antibody production, B cells also present antigen to T cells and produce pro-inflammatory cytokines. Non-targeted immunosuppression has shown efficacy in glomerular disease, but is associated with multiple side effects, and there remains a high proportion of patients with resistant disease. In this manuscript, we will review the biology of antibody secreting cells, and focus on therapeutics that specifically target B cells and plasma cells. We will review B cell depletion strategies, including anti-CD20 monoclonal antibodies, BAFF and APRIL inhibition and B cell receptor inhibition highlighting their role in different glomerular diseases and outline reasons for therapeutic resistance. We will also review plasma cell directed therapies including proteasome inhibition and anti-CD38 therapies, and discuss novel treatments including CAR-T therapy and bispecific T cell engagers.