Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.

Published

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

  • 28232617

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

Digital Object Identifier (DOI)

  • 10.1681/ASN.2016070727

Language

  • eng

Conference Location

  • United States