Heart Transplantation: Immunological Challenges Revisited

Immunologic responses to cardiac allografts initiate before transplantation during brain-dead organ procurement and might persist for years after transplantation, culminating in chronic allograft dysfunction. Despite remarkable advances in post-transplant care and immunosuppressive agents, acute cellular and antibody-mediated rejections as well as chronic allograft vasculopathy significantly affect cardiac allograft and patient survival.

Herein, recent findings of the molecular mechanisms involved in the inflammatory responses before and after heart transplantation, including brain death donor inflammation, acute cellular rejection, antibody-mediated rejection, and chronic allograft dysfunction, have been summarized, along with novel therapeutic approaches for their treatment. Finally, recent developments in prognostic and diagnostic biomarkers for immunological complications have been provided, with an overview of the most promising biomarkers to date.

Due to the recent developments in the description of molecular mechanisms involved in the immunopathogenesis of cardiac allograft rejection, some immune cells, proinflammatory cytokines, and adhesion molecules have been proposed as therapeutic targets for the prevention or treatment of alloimmune responses. In addition, several molecules derived from graft tissue or immune cells, e.g. natriuretic peptides, cardiac troponins, exosomal products, microRNAs, and donor-derived cell-free DNA, have been suggested as potential biomarkers for the prediction or diagnosis of cardiac transplant rejection.

Considering the need to design non-invasive, low-cost tests for early diagnosis of post-transplant complications and convenient follow-up of the cardiac transplant recipients, peripheral blood biomarkers could be appropriate candidates for this purpose.