Humoral rejection in heart transplantation in the current era

Immune response to the human leukocyte antigens (HLA) of a donor heart, resulting in antibody-mediated rejection (AMR), remains one of the greatest challenges in current transplant medicine. Besides the risk of acute functional deterioration of the graft during rejection, there is clear evidence of induction and acceleration of the development of coronary allograft vasculopathy with recurrent or severe AMR and development of donor-specific HLA antibodies. Management guidelines and consensus statements currently have to rely on limited evidence. In this review, we illustrate some of the immune mechanisms underlying AMR, summarize the clinical impact, and discuss the therapy concepts of the recently emerging armamentarium of medical interventions. We also highlight some pitfalls for AMR-therapy protocol design and suggest a staged approach for decision-making at the occurrence of <i>de novo</i> donor-specific antibodies post transplant.