Date: Saturday, May 30, 2020
Session Name: Biomarkers, Immune Assessment and Clinical Outcomes IV
Session Time: 3:15pm-4:45pm
Presentation Time: 3:51pm-4:03pm
*Purpose: Cirrhosis-related immune dysfunction likely contributes to early mortality following liver transplant (LT) resulting from infections. We previously identified a pre-transplant biomarker panel for immune dysfunction – the immune frailty index (IFI). IFI predicts early mortality following LT; however, the mechanism is unknown. Here, we evaluate alterations in recipient CD4+ T cell repertoire and T cell exhaustion as potential causes for immune frailty in LT recipients.
*Methods: Prior analysis demonstrated that HCV viral load, pre-LT plasma Eotaxin, MMP3, and Fractalkine predict 1yr mortality. An immune frailty index (IFI) was created by assigning 1 point for each factor above the median. High IFI pts were matched 1:2 with low IFI pts and healthy controls (HC) based on age, gender, and cause of liver disease. Multiparametric flow cytometric analysis was performed.
*Results: Pts with a low IFI (Score 0-2, N=112) have 95.5% 1yr survival compared with 46.2% for high IFI (Score 3-4, N=13). Cause of death was most commonly sepsis in high IFI; whereas cardiac mortality was more common in low IFI. To augment variability between pts, high IFI (N=4) were matched 1:2 with low IFI (N=7) based on gender, age and cause of liver disease. Demographics were equivalent between groups, except for a trend towards lower Karnofsky score in high IFI (p=0.12). Similar to the larger cohort, matched high IFI more likely developed infections (50% vs 0%, p=0.05). Survival was 50% & 25% at 1- and 2-yrs for IFI high versus 100% at 1- and 2-yrs for IFI low (p=0.02). Both groups exhibit significant decrease in naïve and effector CD4 cells and increase in central memory, effector memory, and regulatory CD4+ T cells compared to HC (p<0.01), but subsets were similar between IFI high and low. Exhausted CD4+ T cell subsets (PD-1+) were more also more frequent in both groups compared with HC, but IFI high demonstrated a significant increase in CD4+ T cell exhaustion amongst central memory (p=0.02) and effector memory CD4+ T cells (p=0.04).
*Conclusions: We have identified pre-transplant Eotaxin, Fractalkine, and MMP3 as potential biomarkers to predict post-transplant mortality. The resulting IFI has potential to identify pts at increased risk for futile outcomes prior to LT and augment clinical assessment among high acuity recipients. Increase in CD4 T cell exhaustion in pts at high risk of immune frailty may contribute to vulnerability of such recipients to infections and other immune related events following LT.
To cite this abstract in AMA style:Lunsford KE, Aware N, Cleveland K, Nguyen DT, Graviss EA, Minze LJ, Eagar TN, Li XC, Ghobrial RM. Evaluation of Pre-Transplant T Cell Exhaustion as a Mechanism for Immune Dysfunction and Recipient Risk of Death Following Liver Transplant [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/evaluation-of-pre-transplant-t-cell-exhaustion-as-a-mechanism-for-immune-dysfunction-and-recipient-risk-of-death-following-liver-transplant/. Accessed September 29, 2020.
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