AI Article Synopsis

  • Current kidney transplant regimens often struggle to prevent antibody-mediated rejection (ABMR) in sensitized individuals, leading to graft failure.
  • Research showed that anti-CD154 monoclonal antibody (mAb) treatment for kidney transplants in nonhuman primates was more effective at controlling rejection and post-transplant immune responses than standard tacrolimus-based therapy.
  • The anti-CD154-treated group had significantly longer survival rates, better suppression of harmful antibodies, and fewer complications post-transplant, suggesting that anti-CD154 mAbs could enhance outcomes in sensitized kidney transplant patients.

Article Abstract

Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)-based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells. After transplant, the nonhuman primates maintained on 5C8-based immunosuppression had significantly better survival compared with those maintained on SOC immunosuppression (135.2 days versus 32.8 days, = 0.013). The 5C8-treated group demonstrated better suppression of DSAs after transplant, more robust suppression of B cell populations, and better induction of regulatory T cells. Fewer infectious and welfare complications, including viral reactivation and weight loss, were also observed with 5C8-based immunosuppression compared with SOC immunosuppression. Therefore, anti-CD154 mAbs may improve kidney transplant outcomes through better control of posttransplant immune responses. The superior efficacy of anti-CD154 mAb-based immunosuppression over tacrolimus-based SOC seen in this highly sensitized NHP transplant model suggests that anti-CD154 mAbs could potentially be used to desensitize and treat highly sensitized patients receiving kidney transplantation.

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Source
http://dx.doi.org/10.1126/scitranslmed.adn8130DOI Listing

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