August 22, 2025Open Access
View Full PaperContemporary Antibody-Mediated Rejection in Heart Transplantation
Structured PICO
P
Population
Heart transplant recipients at risk for or experiencing antibody-mediated rejection (AMR)
I
Intervention
Contemporary diagnostic (e.g., donor-derived cell-free DNA, intragraft gene expression) and therapeutic approaches (e.g., targeting complement-mediated injury, costimulatory blockade, cytokine-mediated inflammatory pathways)
This position statement provides updated guidance on the diagnosis and management of antibody-mediated rejection in heart transplant recipients, highlighting novel molecular diagnostics and targeted therapies.
Abstract
Heart transplantation remains the definitive therapy for patients with advanced heart failure. Acute and chronic rejection affect both short- and long-term outcomes. Antibody-mediated rejection (AMR) remains a leading cause of graft failure and mortality. The reported incidence of AMR varies widely, on the basis of patient characteristics, variability in the interpretation of endomyocardial biopsy, and differences in clinical thresholds at which to treat AMR. There has been increased recognition of the role of human leukocyte antigen donor-specific antibodies and molecular diagnostics, such as donor-derived cell-free DNA or intragraft gene expression, in supporting the diagnosis of AMR beyond histopathology alone. Furthermore, therapeutic management of patients with AMR previously focused on quelling inflammation, removing or neutralizing pathological antibodies, and blocking antibody-producing cells. Novel therapies now also target complement-mediated injury, costimulatory blockade, and specific cytokine-mediated inflammatory pathways. This position statement highlights contemporary diagnostic and therapeutic approaches for AMR after heart transplantation.