Cytomegalovirus-Specific Cell-Mediated Immunity After Prophylaxis Predicts Late-Onset Infection In Lung Transplantation

Background: Cytomegalovirus (CMV) infection remains a prevalent problem in lung transplantation (LT) despite prophylaxis use in seropositive (R+) patients. CMV-specific cell-mediated immunity (CMI) might predict patients at risk. Methods: 60 consecutive R+ LT patients were included. CMV-specific CMI against IE-1 and pp65 was assessed with an ELISPOT assay during prophylaxis and upon its completion. Patients were divided into high (HR) and low risk (LR) according to CMI ROC curves. The primary endpoint was late-onset infection. Results: 31 (52%) patients developed CMV viremia and 1 (2%) developed CMV disease. CMV-specific CMI to IE-1 was significantly lower in those developing CMV infection (120.3±29.3 vs 262.8±313.3, p=0.045). HR patients (<55 spots/200.000 cells for IE-1) showed a significantly higher cumulative incidence of CMV infection (Log-rank=0.020, HR 2.82). Among those with clinically relevant CMV infection (>10000 copies), CMI differences increased (Log-rank=0.012, HR 4.23) (Figure 1). HR patients also showed a higher CMV replication load (62378±76862 vs 8510±12367, p=0.005). Sensitivity, specificity, PPV and NPV of CMV-specific CMI predicting clinically relevant CMV infection was 80%, 56%, 38% and 89% respectively. Conclusions: CMV-specific CMI after prophylaxis withdrawal can discriminate R+ LT patients at different risk of late-onset CMV infection.