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.
Pescovitz
Mark D
MD
Department of Surgery, Indiana University, Indianapolis, IN 46202, USA. mpescov@iupui.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D008212:Lymphocyte Depletion; D000069283:Rituximab; D013997:Time Factors
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007518:Isoantibodies; D000069283:Rituximab