Pathological features of antibody-mediated rejection.

Although cell-mediated rejection has remained the most common form of graft rejection after organ transplantation, antibody-mediated rejection has recently gained much significance in clinical transplantation. New evidence points to an antibody-mediated rejection contributing not only to hyperacute and acute but also to chronic allograft rejection. In addition, in discordant xenotransplantation, severe forms of antibody-mediated rejection, including hyperacute rejection and acute humoral xenograft rejection, represent major immunological barriers to successful xenotransplantation. Antibody-mediated rejection in both allotransplantation and xenotransplantation typically does not respond to conventional anti-rejection therapy, so it has recently been recognized as a major cause of graft loss. Histopathology remains the most definitive and reliable tool for the diagnosis of graft rejection in both allografts and xenografts. In this review, we discuss the concept that microvascular injury is a characteristic feature of antibody-mediated rejection that develops in hyperacute, acute and chronic antibody-mediated rejection in both allografts and discordant xenografts as well as in kidney and heart grafts. We also review work indicating that endothelial cell activation and endothelial cell death in the microvasculature can contribute to ultimate graft loss by triggering capillary destruction, interstitial hemorrhage, and platelet-rich microthrombi in hyperacute and acute antibody-mediated rejection as well as with the formation and progression of fibrotic scars in chronic antibody-mediated rejection.