Predicting Acute Cardiac Allograft Rejection Using Donor and Recipient Gene Expression

Acute rejection in cardiac transplant patients is still a contributing factor to limited survival of the implanted heart. Currently there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplantation acute rejection, which would be of great importance for personalizing immunosuppressive treatment. Within the Biomarkers in Transplantation initiative, the predictive biomarker discovery focused on data and samples collected before or during transplantation such as: clinical variables, genes and proteins from the recipient, and genes from the donor. Based on this study, the best predictive biomarker panel contains genes from the recipient whole blood and from donor endomyocardial tissue and has an estimated area under the curve of 0.90. This biomarker panel provides clinically relevant prediction power and may help personalize immunosuppressive treatment and frequency of rejection monitoring. This study, approved by the Providence Health Care Research Ethics Board and related Ethics Boards, was carried out under the Biomarkers in Transplantation (BiT) initiative on subjects who received a cardiac transplant at St. Paul’s Hospital, Vancouver, British Columbia, and signed consent forms. A total of 18 subjects, for whom recipient whole blood (collected in average within two week before transplant) and donor heart tissue (collected at time of transplant) was available, were selected for blood and tissue-based biomarker discovery. Seven of the 18 patients developed acute rejection [AR; ISHLT grade ≥2R] within the first six months post-transplant while 11 did not [non-AR].