Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Kwun, J; Burghuber, C; Manook, M; Iwakoshi, N; Gibby, A; Hong, JJ; Knechtle, S
Published Date
- July 2017
Published In
Volume / Issue
- 28 / 7
Start / End Page
- 1991 - 1996
PubMed ID
- 28232617
Pubmed Central ID
- PMC5491279
Electronic International Standard Serial Number (EISSN)
- 1533-3450
Digital Object Identifier (DOI)
- 10.1681/ASN.2016070727
Language
- eng
Conference Location
- United States