Abstract 2960: Donor Myocardial Apollon mRNA Expression is an Independent Predictor of Cardiac Allograft Rejection
Acute cellular allograft rejection (ACR) is a significant problem in cardiac transplantation and repeated ACR episodes predispose to cardiac allograft vasculopathy. Prediction of ACR risk at organ harvest would tremendously facilitate donor organ judgment particularly because marginal donors are being increasingly accepted due to donor organ shortage. ACR is evidently associated with apoptosis and Apollon is an inhibitor of apoptosis that promotes cell survival. Whether donor myocardial tissue Apollon mRNA could predict ACR in cardiac transplantation is unclear. In a prospective study, left ventricular biopsies (LVBs; n = 1275) were obtained from donors before and after aortic cross-clamping and at 10, 30 and 60 minutes following reperfusion. Tissue Apollon mRNA expression was examined by real time RT-PCR and correlated to later ACR episodes. ACR was defined histologically in 172 endomyocardial biopsies (EMBs) using the guidelines of International Society for Heart and Lung Transplantation. Moderate (1R) and severe (2R and 3R) ACR was diagnosed in 126 and 46 EMBs, respectively. Apollon myocardial expression was significantly decreased before aortic cross-clamping in donors (p = 0.001) and at 10 min reperfusion (p < 0.001) in patients who developed severe as compared to moderate or no ACR. In receiver operating characteristic curve analysis and at a cut-off level of 20.11 arbitrary units, Apollon mRNA expression before aortic cross-clamping in donors identified severe ACR with a sensitivity of 100% and a specificity of 90% (p = 0.0001, AUC = 0.835); and Apollon levels at 10 min reperfusion identified severe ACR with a sensitivity of 100% and a specificity of 95% (p = 0.0001, AUC = 0.796). Tissue Apollon mRNA expression levels at 30 and 60 min reperfusion did not correlate with ACR episodes. These results indicate that Apollon is a sensitive and specific predictor of ACR in cardiac transplantation and might be beneficial in donor selection.