title: Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.
abstract: The efficacy of bortezomib monotherapy in desensitizing kidney transplant candidates with preformed donor-specific antibodies remains unclear. We evaluated the effect of bortezomib on preformed antibodies and upstream components of the B cell response in a primate model sensitized by fully mismatched allogeneic skin transplants to provide mechanistic insights regarding the use of bortezomib as a means of desensitization. Bortezomib treatment given intravenously twice weekly for 1 month (1.3 mg/m2per dose) clearly reduced the numbers of antibody-producing cells and CD38+CD19+CD20-plasma cells in the bone marrow (P<0.05), but donor-specific alloantibody levels did not decrease. We observed a rapid but transient induction of circulating IgG+B cells and an increased number of proliferating B cells in the lymph nodes after 1 month of treatment. Notably, bortezomib treatment induced germinal center B cell and follicular helper T cell expansion in the lymph nodes. These data suggest that bortezomib-induced plasma cell depletion triggers humoral compensation.
authors.affiliation: Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, North Carolina.|Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Jean
authors.initials: J
authors.lastname: Kwun
authors.affiliation: Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.|Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria; and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Burghuber
authors.affiliation: Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Miriam
authors.initials: M
authors.lastname: Manook
authors.affiliation: Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Neal
authors.initials: N
authors.lastname: Iwakoshi
authors.affiliation: Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Gibby
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Hong
authors.affiliation: Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, North Carolina; stuart.knechtle@dm.duke.edu.|Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Knechtle
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D000069286:Bortezomib / Q000494:pharmacology*; D056724:Immunity, Humoral / Q000187:drug effects* / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D014181:Transplantation Immunology / Q000187:drug effects
chemical_list: D000069286:Bortezomib
keywords: Bortezomib; Desensitization; alloantibody; antibody mediated rejection; nonhuman primate