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/m 2 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.