Acute Humoral Rejection of Renal Transplants in Alloimmunized Pigs

Abstract

Despite progress in immunosuppression, acute humoral rejection (AHR) remains an unsolved issue in transplantation, with a possible reversibility in only about 50% of cases. AHR is characterized by antidonor antibodies in the recipient circulation and characteristic histological lesions within the graft itself, as well as complement degradation products and immunoglobulins (IgM and IgG) deposition in vascular zones. The lack of a large animal models of AHR in experimental allotransplantation led us to establish such a model in the pig. Pigs were immunized with peripheral blood mononuclear cells from allogeneic donors and subsequently received a kidney from the same donor, once antidonor antibodies (Ab) had reached a plateau. The efficiency of the alloimmunization, the nature of the induced antibodies and rejection were studied. Six out of seven recipients developed specific antidonor Ab. Three days post-transplantation, characteristic lesions of AHR were observed together with intragraft IgG, IgM, and complement deposition. The AlloAb were found to be cytotoxic and directed against donor MHC class I molecules. We described, for the first time, a large animal model of AHR, which will enable us to more extensively study phenomena implicated in AHR and to test new strategies aimed at its prevention or cure, as well as improve transplant protocols in the case of presensitized or hyperimmunized patients.