A Novel Immune Function Biomarker Predicts Early Clinical Outcomes Following Liver Transplantation.

Abstract

Immune function monitoring post liver transplantation (OLTx) remains substandard. QuantiFERON-Monitor (QFM, Qiagen, USA) is a novel immune function biomarker based on the same laboratory platform as the readily used QFN-gold assay (Qiagen, USA) and measures IFN-γ production after overnight stimulation of 1mL whole blood with both innate (R848) and adaptive (CD3) immune ligands with potential for next-day results. We present a blinded, prospective, observational study, representing the first clinical use of QFM in predicting clinical outcomes post-OLTx. QFM was examined in 69 adult OLTx recipients at the following time-points: pre-OLTX and post-OLTx days 1,3,5, 7, 14 and 30. Patients were monitored for treated and biopsy proven acute rejection (tBPAR) (n=17 (24.6%) median 9 days) and infections (n=21 (30.4%) median 12 days). QFM fell post-OLTx to a nadir at D3, then gradually increased to D30 (p<0.0001). Elevated D7 QFM in clinically stable patients (n=57, median 1.35IU/mL) was significantly associated with future tBPAR (ROC 0.84, p<0.0001), conversely low QFM was associated with infection (ROC 0.74, p=0.008). In those with the most impaired immune response (bottom quartile, <0.62IU/mL) 0/15 (0%) developed tBPAR, whilst 6/15 (40%) developed an infection. Conversely, in those with a robust immune response (upper quartile, >4.0IU/mL) 8/14 (57%) developed tBPAR whilst only 1/14 (7%) developed an infection.Figure: No Caption available.Notably, 4 of 5 patients with the lowest QFM developed opportunistic infections including cryptococcal meningitis, HSV and fungal peritonitis. Importantly, therapeutic drug levels at each time point were not associated with QFM or clinical events. D7 QFM predicts early post-OLTx clinical events, particularly identifying patients (QFM <1.35IU/mL) who are at risk of infection with a low probability of rejection, who may benefit from immunosuppression reduction. This may facilitate individualisation of immunosuppression and fundamentally alter the management of OLTx, and possibly other solid organ recipients. DISCLOSURE:Sood, S.: Grant/Research Support, Cellestis. Yu, J.: Employee, Cellestis Ltd, (Past). Visvanathan, K.: Grant/Research Support, Cellestis Ltd. Testro, A.: Grant/Research Support, Cellestis Ltd.