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Molecular targets on B-cells to prevent and treat antibody-mediated rejection in organ transplantation. Present and Future

ABSTRACT Introduction: Waiting lists for transplant are increasing day after day since transplantation is still the best option for the treatment of end-stage organ failure. Likewise, our increasing knowledge about how immune system mounts the response against allograft is at the point that up to 95% of acute T-cell-mediated rejections are effectively controlled by current immunosuppressive therapy. Nevertheless, this is not the case for acute and chronic antibody-mediated rejections (ABMR), where treatments to reduce the level of donor specific antibodies (DSAs) remain suboptimal, causing the majority of acute and chronic graft losses. Areas covered: T-cell immunosuppressant agents are usually ineffective to treat humoral rejection and current strategies to prevent ABMR include plasmapheresis; high doses of intravenous immunoglobulin; anti-CD20 monoclonal antibodies to treat B-cells; and in some cases Bortezomib, which mainly affects plasmoblast and plasma cells, or antibodies against components of complement cascade. Expert Opinion: We reassess the B-cell ontogeny in order to propose new molecular targets that interrupt the antibody production pathways and their eventual pathological injury. We also take a look at the pharmaceutical industry to find agents that are currently being assayed for B-cell pathologies and that could be used in the future to prevent and treat ABMR.