title: Proteasome inhibitor treatment of antibody-mediated allograft rejection.
abstract: OBJECTIVE
  Bortezomib is a first-in-class proteasome inhibitor that was originally Food and Drug Administration approved for the treatment of multiple myeloma. In the past few years, off-label use in solid organ transplant recipients has demonstrated its ability to provide plasma cell-targeted therapy in humans. The purpose of this review is to provide an update of recent basic science and clinical results with bortezomib in treating antibody-mediated rejection (AMR) that occurs in solid organ transplant recipients.
  
  
  RESULTS
  Proteasome inhibitor therapy for AMR in kidney transplant recipients is effective both as primary and as rescue therapy. Optimal responses with proteasome inhibitor therapy are obtained when AMR is diagnosed promptly and early in the posttransplant period. However, proteasome inhibitor therapy for late AMR (i.e., occurring 6 months or later posttransplant) provides less predictable results, likely due to the existence of a substantial bone marrow niche-resident long-lived plasma cell population. Proteasome inhibitor therapy has also recently been shown to provide effective therapy for AMR in heart, and also, transplant recipients.
  
  
  CONCLUSIONS
  Proteasome inhibitor therapy with bortezomib provides effective treatment for AMR in solid organ transplant recipients. As the first plasma cell-targeted therapy, proteasome inhibitor therapy provides the additional advantage of opening new possibilities for biologically defined plasma cell-targeted therapies.
authors.affiliation: Division of Transplantation, Department of Surgery, Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA. woodlees@uc.edu
authors.forename: E Steve
authors.initials: ES
authors.lastname: Woodle
authors.forename: Rita R
authors.initials: RR
authors.lastname: Alloway
authors.forename: Alin
authors.initials: A
authors.lastname: Girnita
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D006084:Graft Rejection / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D006648:Histocompatibility / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology; D016377:Organ Transplantation / Q000009:adverse effects; D010950:Plasma Cells / Q000187:drug effects* / Q000201:enzymology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D023001:Transplantation Tolerance / Q000187:drug effects; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D006680:HLA Antigens; D007155:Immunologic Factors; D007518:Isoantibodies; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex