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.