Pre-transplant T-cell Clonality: A Biomarker For Prediction Of Sepsis In Liver Transplant Recipients
*Steven L Jones, *Linda W Moore, *Xian C Li, *Edward A Graviss, *Duc T Nguyen, *Ashish Saharia, *Constance Mobley, *Mark Hobeika, *Robert McMillan, *Joy Nolte Fong, *Laurie Minze, Ahmed O Gaber, R Mark Ghobrial
Houston Methodist Hospital, Houston, TX
OBJECTIVE(S): Sepsis is a major healthcare issue. It is the leading cause of death in liver transplant (LT) recipients. Currently, there are no biomarkers to predict sepsis prior to manifestation of clinical symptoms. This study determined the ability of increased pre-transplant T-cell clonality to predict sepsis development after LT.
METHODS: Between 12/2013-3/2018, we performed 465 LTs. After excluding patients with extended criteria donors, multi-organ, re-transplantations, or autoimmune disease, 180 consecutive LT were enrolled. T-cell characterization was assessed using immunoSEQ Assay <48hrs prior to LT. Sepsis-2 and Sepsis-3 cases were identified by chart review. ROC determined optimal T-cell clonality for predicting post-LT sepsis. Kaplan-Meier and Cox-proportional hazard modeling assessed outcome-associated prognostic variables.
RESULTS: Patients with baseline T-cell clonality ≥0.072 were 3.82 (1.25, 11.40), p=0.02) and 2.40 (1.00, 5.75; p=0.049) times more likely to develop 90-day and 1-year post-LT sepsis, respectively, when compared to recipients with lower (<0.072) clonality.
T-cell clonality was the only predictor of 90-day post-LT sepsis in multivariable analysis (C Statistic = 0.75). Adequate treatment resulted in equivalent survival rates between both groups (93.6% vs. 96.2% p=0.41) at 1-year.
CONCLUSIONS: T-cell clonality is a novel biomarker predictor of sepsis prior to the development of clinical symptoms. Early sepsis monitoring and management likely reduced post-LT mortality. These findings may have significant implications for developing sepsis-prevention protocols in transplantation and potentially other surgical procedures.
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