Cardiac allograft rejection is a serious concern in transplant medicine, conferring an increased risk of acute graft failure and adverse patient outcomes. The guideline-directed histologic grading of biopsy tissues for rejection surveillance has modest diagnostic performance, correlating poorly with the clinical trajectory of concurrent rejection events and offering minimal information about future rejection risk. These limitations expose patients to an immediate potential risk of over- or under-treating for rejection, while also imposing a rigid, protocolized rejection surveillance and immunosuppression weaning strategy that appears outdated in an era of precision medicine.

 

These findings highlight the limitations of the current guideline-recommended biopsy grading standard, while supporting the diagnostic and prognostic importance of the PD1/PD-L1 checkpoint system and regulatory T-cells in cardiac allografts. We believe that the results of this proof-of-concept work will lead to a rethinking of rejection surveillance protocols for heart transplant patients, and may represent an initial step towards identifying molecular targets for immunotherapeutics in transplant medicine.

 

 

Learning Objectives: