Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 28, Issue 7, Pages 1991-1996Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2016070727
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Funding
- National Institutes of Health [U19AI051731]
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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/m(2) per dose) clearly reduced the numbers of antibody-producing cells and CD38(+)CD19(+)CD202 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.
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