Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

Published 2 April 2015

Monica M. Colvin, Jennifer L. Cook, Patricia Chang, Gary Francis, Daphne T. Hsu, Michael S. Kiernan, Jon A. Kobashigawa, JoAnn Lindenfeld, Sofia Carolina Masri, Dylan Miller, John O’Connell, E. Rene Rodriguez, Bruce Rosengard, Sally Self, Connie White-Williams, Adriana Zeevi

Circulation. 2015 May; 131(18): 1608-39

• Advanced Heart Failure & Transplantation
• Cardiology
• Cardiothoracic Surgery
• Endorsement
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Antibody-mediated rejection (AMR) of the cardiac allograft is a poorly defined and challenging diagnosis for transplant recipients and their clinicians. Although even its very existence in heart transplantation was debated until relatively recently, improved immunopathologic and serological techniques to detect myocardial capillary complement deposition and circulating anti-HLA (human leukocyte antigen) antibodies have led to the detection of a spectrum of newly uncovered immunologic changes that characterize AMR.

The earliest standardized clinical and pathological criteria for the diagnosis of AMR in heart transplantation became available in 2004, the result of a task force assembled by the International Society for Heart and Lung Transplantation (ISHLT). In 2006, the criteria were refined by the ISHLT Immunopathology Task Force to provide 4 categories of diagnostic criteria: clinical, histopatic, immunopathic, and serological. However, despite these published criteria, currently >50% of heart transplant centers make the diagnosis of AMR based on cardiac dysfunction and the lack of cellular infiltrates on the heart biopsy.

More recently, the ISHLT Consensus Conference on AMR redefined the pathological diagnosis of AMR in the 2013 ISHLT Working Formulation for the Standardization of Nomenclature in the Pathologic Diagnosis of Antibody-Mediated Rejection in Heart Transplantation, which is anticipated to reduce variations in the diagnosis of AMR, providing a platform for the development of standardized therapies. 

The goal of the present scientific statement is to provide the heart transplant professional with an overview of the current status of the diagnosis and treatment of AMR in the cardiac allograft based on recent consensus conferences and the published literature, and includes recommendations to facilitate evolving standardization and strategies for future study.

This statement was endorsed by ISHLT in 2015.

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