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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/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.

SUBMITTER: Kwun J

PROVIDER: S-EPMC5491279 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.

Kwun Jean J Burghuber Christopher C Manook Miriam M Iwakoshi Neal N Gibby Adriana A Hong Jung Joo JJ Knechtle Stuart S

Journal of the American Society of Nephrology : JASN 20170223 7

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 ...[more]

PMID: 28232617

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Project description:INTRODUCTION:In this study we developed the Disability Beliefs Scale to assess Veterans' beliefs that engaging in treatment, as well as other behaviors, would affect the likelihood of a Veteran's being awarded disability-related benefits. We posited that Veterans with stronger beliefs that attending mental health treatment would facilitate a service-connection award would be more likely to attend PTSD treatment before their compensation and pension examinations for PTSD. METHODS:Electronic health records for 307 post-9/11-era Veterans applying for compensation and pension for service-connected PTSD and engaging in a clinical trial of a treatment-referral intervention were analyzed for PTSD-specific and more general mental health treatment use around the time of their compensation examinations. All participants completed the Disability Beliefs Scale and other baseline assessments. Multilevel models assessed change in treatment use as a function of time relative to the C&P exam, compensation examination status (before or after), and the interaction between examination status and beliefs about treatment benefits. RESULTS:No main effects of time or examination status were observed. As hypothesized, beliefs about treatment benefits moderated the effect of examination status on PTSD treatment use. Veterans believing more strongly that mental health treatment would help a claim differentially attended PTSD treatment before the examination than after. The effect was not observed for general mental health treatment use. CONCLUSION:The association between Veterans' use of PTSD treatment and their service-connection examination status was moderated by beliefs that receiving treatment affects the service-connection decision. This suggests that factors reported to motivate seeking service-connection-finances, validation of Veterans' experiences, and the involvement of significant others-might also help motivate Veterans' use of effective PTSD treatments. However, the results reflect correlations that could be explained in other ways, and service-connection was one of many factors impacting PTSD treatment engagement.

Dataset Information

Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.

Publications

Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients.

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