Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients
Jean Kwun, Christopher Burghuber, Miriam Manook, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Stuart Knechtle, Jean Kwun, Christopher Burghuber, Miriam Manook, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Stuart Knechtle
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/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.
Copyright © 2017 by the American Society of Nephrology.
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Source: PubMed