Targeting B cells in sensitized kidney transplant patients: state of the art and future perspectives

Purpose of review In sensitized kidney transplant recipients, whose number is continuously growing, the negative impact of antibody-mediated rejection is being increasingly recognized. The purpose of this review is to summarize the state of knowledge about the mechanisms of alloantibody production. We will also report the most recent clinical results of current immunosuppressive protocols - either preventive or curative - in this population. Recent findings Even if progress in access to transplantation and short-term graft survival has been made in sensitized patients using therapeutic strategies targeting both alloantibodies (plasmapheresis and/or intravenous globulins) and B cells (CD20 antibodies), antibody-mediated rejection remains a critical issue frequently compromising renal function and middle-term graft survival. The partial efficacy of such strategies and the presence in sensitized patients of both peripheral memory B cells and bone marrow plasma cells capable of alloantibody synthesis in vitro suggest that, in vivo, alloantibody production most likely involves both cell types, not equally targeted by CD20 antibody-based therapies. Summary The need for improved strategies of prevention/treatment of antibody-mediated rejection, have led, based on the actual understanding of alloantibody synthesis, to the use of drugs targeting plasma cells, that is proteasome inhibitors. Preliminary results are contrasted and highlight the necessity for controlled studies in the field of antihumoral therapies.