A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation

Abstract

Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon gamma (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. 75 adult transplant recipients were prospectively monitored in a blinded, observational study. 55/75 (73.3%) patients experienced a total 89 clinical events. Most events occurred within the first month. Low week 1 (W1) results were significantly associated with risk of early infection (AUROC 0.74, p=0.008). IFNγ≤1.30IU/mL (LR+ 1.93, sensitivity 71.4%, specificity 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ≤1.30IU/mL. Moreover, an elevated W1 result was significantly associated with the risk of rejection within the first month post-transplant (AUROC 0.77, p=0.002), but no episodes of infection. On multivariate logistic regression, IFNγ≥4.49IU/mL (OR 4.75) may be an independent predictor of rejection (p=0.05). CONCLUSION: Low IFNγ suggesting over-suppression is associated with infections, while high IFNγ indicating under-suppression is associated with rejection. This assay offers the potential to allow individualisation and optimisation of immunosuppression that could fundamentally alter the way patients are managed following transplantation. This article is protected by copyright. All rights reserved.