Histopathology of discordant xenotransplantation

Abstract

Purpose of review The combination of improved regimens of immunosuppression and supportive therapies with sustained depletion of native xenoreactive antibodies that bind to donor antigens, or with genetic deletion of donor antigens, has resulted in a significant extension of graft survival in large animal models of discordant xenotransplantation. This review focuses on organ transplantation in the pig-to-nonhuman primate and summarizes a shifting pattern of histopathologic findings associated with xenograft rejection. Recent findings Hyperacute rejection is preventable in renal and cardiac xenografts but still problematic in pulmonary xenografts. Interstitial mononuclear cell infiltrates of acute cellular rejection are no longer prominent in xenografts with prolonged survival. Acute humoral xenograft rejection has been modulated in xenograft kidneys and hearts and now involves thrombotic microangiopathy as a major feature. Graft vasculopathy typical of chronic rejection has only recently been identified. Summary For most discordant xenografts, thrombotic microangiopathy challenges our understanding of acute humoral xenograft rejection, the main cause of xenograft failure. Chronic rejection may be the next hurdle in xenotransplantation. As xenograft survival is prolonged, an ongoing scrutiny of the histologic features of these grafts will be crucial to our ability to characterize the pathophysiologic mechanisms of xenograft rejection or tolerance.