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Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.

Publication ,  Journal Article
Kwun, J; Burghuber, C; Manook, M; Iwakoshi, N; Gibby, A; Hong, JJ; Knechtle, S
Published in: J Am Soc Nephrol
July 2017

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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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

July 2017

Volume

28

Issue

7

Start / End Page

1991 / 1996

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transplantation Immunology
  • Male
  • Macaca mulatta
  • Immunity, Humoral
  • Bortezomib
  • B-Lymphocytes
  • Animals
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

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Kwun, J., Burghuber, C., Manook, M., Iwakoshi, N., Gibby, A., Hong, J. J., & Knechtle, S. (2017). Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients. J Am Soc Nephrol, 28(7), 1991–1996. https://doi.org/10.1681/ASN.2016070727
Kwun, Jean, Christopher Burghuber, Miriam Manook, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, and Stuart Knechtle. “Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.J Am Soc Nephrol 28, no. 7 (July 2017): 1991–96. https://doi.org/10.1681/ASN.2016070727.
Kwun J, Burghuber C, Manook M, Iwakoshi N, Gibby A, Hong JJ, et al. Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients. J Am Soc Nephrol. 2017 Jul;28(7):1991–6.
Kwun, Jean, et al. “Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.J Am Soc Nephrol, vol. 28, no. 7, July 2017, pp. 1991–96. Pubmed, doi:10.1681/ASN.2016070727.
Kwun J, Burghuber C, Manook M, Iwakoshi N, Gibby A, Hong JJ, Knechtle S. Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients. J Am Soc Nephrol. 2017 Jul;28(7):1991–1996.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

July 2017

Volume

28

Issue

7

Start / End Page

1991 / 1996

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transplantation Immunology
  • Male
  • Macaca mulatta
  • Immunity, Humoral
  • Bortezomib
  • B-Lymphocytes
  • Animals
  • 3202 Clinical sciences
  • 1103 Clinical Sciences