B cells: a rational target in alloantibody-mediated solid organ transplantation rejection

Loss of allografts over time remains a barrier to achieving successful outcomes in solid organ transplantation. Although the role of donor-specific alloantibody-mediated mechanisms in hyperacute rejection is well known, research and management of early and late post-transplant rejection have traditionally focused on T cell-mediated mechanisms. However, available agents that affect T-cell pathways have minimal impact on long-term graft survival, suggesting that other effector mechanisms are involved. A growing body of evidence now supports a role for alloantibody-mediated mechanisms in early and late graft rejection, which can significantly impact on long-term graft survival. The important role of B cells in generating and perpetuating alloantibody production provides a rationale for B-cell depletion therapy as an approach to prevent or reduce alloantibody formation before transplantation and to treat or prevent early and late alloantibody-mediated rejection. The use of monoclonal antibodies that directly target B cells, in combination with standard alloantibody-depleting therapies and/or immunosuppression, has been investigated in several small non-controlled studies. Promising results suggest that this strategy warrants further investigation in larger controlled studies.