Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.
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.
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Related Subject Headings
- Urology & Nephrology
- Transplantation Immunology
- Male
- Macaca mulatta
- Immunity, Humoral
- Bortezomib
- B-Lymphocytes
- Animals
- 3202 Clinical sciences
- 1103 Clinical Sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Urology & Nephrology
- Transplantation Immunology
- Male
- Macaca mulatta
- Immunity, Humoral
- Bortezomib
- B-Lymphocytes
- Animals
- 3202 Clinical sciences
- 1103 Clinical Sciences