Evaluation of global immune biomarkers to predict infections in lung transplant recipients

Background: Immune biomarkers could assess levels of immunosuppression and predict infections in transplant recipients. We aimed to evaluate the absolute lymphocyte count (ALC), absolute neutrophil count (ANC), Quantiferon-Monitor and the mitogen component of the Quantiferon-CMV assay alone and combined to predict serious opportunistic infections (SOI) in lung transplant recipients. Methods: Patients were prospectively recruited from 2015–17, with blood collected at 3, 6 and 12 months post-transplant. Infections were classified as SOI if requiring hospitalization and caused by an opportunistic pathogen. Logistic regression was used to calculate odds ratios (OR). Results: Within 18 months post-transplant, 35/80 patients experienced 46 SOI's. Low ALCs were associated with SOI between 3–6 (median 1.4 vs. 1.0×1000 cells/µL, OR 5.38 per unit decrease, 95% CI 1.38–21.02, p = 0.02) and 6–12 (1.3 vs. 0.8×1000 cells/µL, OR 3.48, 95% CI 1.20–10.1, p = 0.02) months. Mitogen values were significantly lower with SOI between 3–6 months (5.8 vs. 0.3 IU/mL, OR 0.78, 95% CI 0.63–0.97, p = 0.02). Area under the ROC curve for all biomarkers combined were modestly higher compared to ALC alone. Negative predictive values were high. Conclusions: Immune biomarkers have the potential to measure net immunosuppression and identify transplant recipients at higher risk for SOI. ALC was the most useful single test although incorporating 3 other biomarkers modestly improved predictions. Negative predictive values were high indicating that patients with high ALC values were unlikely to experience SOI. While this approach could inform decision-making regarding immunosuppression dosing, intensity of monitoring and antimicrobial prophylaxis, further research is required before clinical implementation.