Immunological challenges of cardiac transplantation: The need for better animal models to answer current clinical questions

Introduction: In the last decade, two advances have shifted attention from cellular rejection to antibody-mediated rejection (AMR) of cardiac transplants. First, more sensitive diagnostic tests for detection of AMR have been developed. Second, improvements in immunosuppression have made severe acute cellular rejection uncommon, but have had less effect on AMR. Discussion: Antibodies can contribute to graft rejection by activation of complement, by activation of vascular endothelial and smooth muscle cells, and by activation of neutrophils, macrophages or natural killer cells. Because acute rejection is a risk factor for chronic rejection in all types of organ transplants, it is has been proposed that AMR can cause chronic rejection. Conclusion: Small animal models need to be developed to gain further insights into AMR and the role of antibodies in chronic graft arteriopathy. This article reviews the current clinical data and existing mouse models for AMR.