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Desensitization for Deceased Donor Transplantation: Testing a New Paradigm in the Nonhuman Primate

Z. W. Fitch, R. Schmitz, P. M. Schroder, M. Manook, A. Y. Choi, J. Yoon, J. Kwun, S. J. Knechtle

Duke University, Durham, NC

Meeting: 2020 American Transplant Congress

Abstract number: 541

Keywords: Alloantibodies, Co-stimulation, Sensitization, T helper cells

Session Information

Session Name: B-cells / Antibodies /Autoimmunity

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:27pm-3:39pm

Location: Virtual

*Purpose: Desensitization regimens have rarely been applied to deceased donor allotransplantation. We hypothesized that belatacept monotherapy during a simulated deceased donor waiting list period would improve graft survival in sensitized nonhuman primates desensitized with carfilzomib and belatacept prior to the waiting list period.

*Methods: Rhesus macaques (n=7) were sensitized to maximally MHC-mismatched donors with two sequential skin transplants, then desensitized with carfilzomib and belatacept. This was followed by a simulated waiting list period of 3 months, during which time 3 animals received belatacept monotherapy (Desensitization + Prolonged Belatacept) and 4 received no additional treatment (Desensitization Alone). Animals then received life-sustaining kidney transplants from their MHC-mismatched skin donors and received rhesus-specific antithymocyte globulin induction and standard triple immunosuppression. One animal was excluded from post-transplant analysis due to a technical complication.

*Results: Compared to animals treated with Desensitization Alone, animals treated with Desensitization + Prolonged Belatacept showed improved graft survival (p<0.05, Figure 1A), a delayed post-transplant rebound in donor-specific antibody (Figure 1B), and a more profound reduction of lymph node Tfh cells during the pre-transplant treatment period (p<0.01, Figure 1C). Tfh cells repopulated after belatacept cessation and kidney transplantation (p<0.05, not shown).

*Conclusions: Belatacept monotherapy during a simulated waitlist period was associated with improved graft survival in previously desensitized nonhuman primates and suggests a strategy for applying clinical desensitization regimens to deceased donor transplantation. Post-transplant rebound of both donor-specific antibody levels and Tfh cells suggest that alternative maintenance immunosuppression regimens that better control the germinal center response may further improve outcomes.

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To cite this abstract in AMA style:

Fitch ZW, Schmitz R, Schroder PM, Manook M, Choi AY, Yoon J, Kwun J, Knechtle SJ. Desensitization for Deceased Donor Transplantation: Testing a New Paradigm in the Nonhuman Primate [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/desensitization-for-deceased-donor-transplantation-testing-a-new-paradigm-in-the-nonhuman-primate/. Accessed June 6, 2025.

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