Evaluation of Global Immune Biomarkers to Predict Infections in Lung Transplant Recipients

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.

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).

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.

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.