Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients

J Am Soc Nephrol. 2017 Jul;28(7):1991-1996. doi: 10.1681/ASN.2016070727. Epub 2017 Feb 23.


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/m2 per 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.

Keywords: Bortezomib; Desensitization; alloantibody; antibody mediated rejection; nonhuman primate.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • Bortezomib / pharmacology*
  • Immunity, Humoral / drug effects*
  • Immunity, Humoral / physiology
  • Macaca mulatta
  • Male
  • Transplantation Immunology / drug effects


  • Bortezomib