Antibody-Mediated Graft Rejection in Nonhuman Primate Models: Comparison of Sensitized Allotransplant and Xenotransplant Rejection
Antibody-mediated rejection (AMR) is a barrier to successful long-term xenograft survival. We compared AMR in kidney xenotransplantation to sensitized kidney allotransplantation in a nonhuman primate model. With conventional CNI-based immunosuppressive maintenance, both groups showed limited graft survival with strong antibody-mediated rejection features, such as interstitial hemorrhage, thrombotic microangiopathy, peritubular capillaritis, and glomerulitis, without T-cell-mediated rejection. The strong similarity between sensitized allo- and unsensitized xeno-rejection suggests a possible common mechanism of rejection in xeno and sensitized allotransplantation. Further investigation is warranted to evaluate desensitization strategies that have shown efficacy in an allosensitized setting to determine if they may apply as well to xenotransplantation. It would also be important to determine whether allosensitized hosts are also primed to xeno-AMR and, vice versa, whether xenotransplantation primes the immune response to allo-AMR.
