Evaluation of Quantiferon®-Monitor as a biomarker of immunosuppression and predictor of infection in lung transplant recipients.

Abstract

Optimizing immunosuppression in lung transplant recipients (LTR) is crucially important in minimizing the risk of infection and rejection. Quantiferon®-Monitor (QFM) is a candidate immune function biomarker which has not yet been rigorously evaluated in the lung transplant setting. The aim of this prospective cohort study was to explore relationships between QFM results, immunosuppression, and infection/rejection in LTR. QFM, which measures interferon-γ after stimulation with innate and adaptive immune antigens, was tested before and at 2, 6, 12, 24 and 52weeks post-transplant. Immunosuppression relationships were assessed with linear mixed effects models. Clinical outcomes were analyzed based on the preceding QFM result. Eighty LTR were included. Median pre-transplant QFM levels were 171IU/mL (IQR 45-461), decreasing to 3IU/mL (IQR 1-8) at 2weeks post-transplant then progressively recovering toward baseline with time from transplant. Prednisolone was strongly inversely associated with QFM level (0.1mg/kg dose increase correlating with 88IU/mL QFM decrease, 95% CI 61-114, P<.001). Patients with QFM values <10 and <60IU/mL were more likely to develop a serious opportunistic infection between 3 and 6months (HR 6.38, 95% CI 1.37-29.66, P=.02) and 6-12months (HR 3.25, 95% CI 1.11-9.49, P=.03) post-transplant, respectively. QFM values declined significantly post-transplant, with patients recovering at different rates. Prednisolone dose significantly impacted QFM results. Low levels were associated with infection beyond 3months post-transplant, suggesting that QFM may be able to identify overly immunosuppressed patients who could be targeted for dose reduction. Larger prospective studies are needed to further evaluate this promising assay.