Background: Endomyocardial biopsy (EMB) is the "gold standard" in cardiac allograft acute cellular rejection (ACR) diagnosis, but it is invasive. ACR prediction at organ harvest could reduce EMB frequency in low-risk recipients. ACR is reportedly associated with apoptosis and Apollon inhibits apoptosis and promotes cell survival. It is unknown whether donor myocardial tissue Apollon mRNA could predict ACR.
Methods: Left ventricular biopsies (LVBs) were obtained from 336 donors before and after aortic cross-clamping (ACC) and at 10, 30 and 60 minutes of reperfusion in recipients. Tissue Apollon messenger RNA (mRNA) expression was examined by real-time reverse transcript-polymerase chain reaction (RT-PCR) and correlated with ACR episodes.
Results: Apollon LVB expression was significantly decreased before and after ACC in donors and at 10 minutes of reperfusion (p < or = 0.0233) in recipients who developed Grade 2R and 3R ACR as compared with those with Grade 1R or no ACR. In addition, Apollon myocardial expression was significantly decreased at 10 minutes of reperfusion in patients who developed Grade 3R ACR compared with all other ACR grades (p < or = 0.0425). In receiver-operating characteristic curve analysis, at a cut-off level of 75.66 arbitrary units, Apollon mRNA before ACC in donors identified combined Grade 2R and 3R ACR with a sensitivity of 94% and a specificity of 96% (p < 0.0001; area under the curve [AUC] = 0.965; odds ratio [OR] = 0.958; 95% confidence interval [CI] 0.942 to 0.974).
Conclusions: Apollon is a sensitive and specific predictor of ACR in donated cardiac allografts and may have important implications in the choice of surveillance.