Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study

Abstract Background Natural killer (NK) cells play a major role in immune tolerance after sepsis, and the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system mediates evasion of host immunity. The correlation between PD-L1 levels in NK cells and the prognosis of patients...

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Main Authors: Wenqiang Jiang, Xusheng Li, Miaoyun Wen, Xiaoyu Liu, Kangrong Wang, Qiaosheng Wang, Ya Li, Maohua Zhou, Mengting Liu, Bei Hu, Hongke Zeng
Format: Article
Language:English
Published: BMC 2020-10-01
Series:Critical Care
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13054-020-03329-z
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author Wenqiang Jiang
Xusheng Li
Miaoyun Wen
Xiaoyu Liu
Kangrong Wang
Qiaosheng Wang
Ya Li
Maohua Zhou
Mengting Liu
Bei Hu
Hongke Zeng
author_facet Wenqiang Jiang
Xusheng Li
Miaoyun Wen
Xiaoyu Liu
Kangrong Wang
Qiaosheng Wang
Ya Li
Maohua Zhou
Mengting Liu
Bei Hu
Hongke Zeng
author_sort Wenqiang Jiang
collection DOAJ
description Abstract Background Natural killer (NK) cells play a major role in immune tolerance after sepsis, and the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system mediates evasion of host immunity. The correlation between PD-L1 levels in NK cells and the prognosis of patients with sepsis, however, has not been elucidated. Thus, it was hypothesized that PD-L1 in NK cells could be a novel biomarker of the mortality for sepsis patients. Methods A prospective, observational, cohort study in a general intensive care unit had earlier enrolled patients according to the sepsis-3 criteria, and peripheral blood samples were collected within 24 h post-recruitment. The expression of four co-signaling molecules (PD-1, CD28, PD-L1, and CD86) in NK cells was assayed, and the sequential organ failure assessment (SOFA) scores were recorded on day 1. Patients were followed up until 28 days. Multivariate regression analysis assessed the independent risk factors for 28-day mortality. The association between biomarkers and 28-day mortality was assessed by Cox regression survival analysis. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results A total of 269 patients were recruited, and 114 patients were finally included for final analysis. Of these, 30 (26.3%) patients died during 28 days. The percentage of PD-L1+ NK cells (OR 1.022; 95% CI 1.002–1.043) and SOFA scores (OR 1.247; 95% CI 1.092–1.424) were independent risk factors for 28-day mortality. The AUC of the percentage of PD-L1+ NK cells, SOFA scores, and their combination model were 0.655 (0.559–0.742), 0.727 (0.635–0.807) and 0.808 (0.723–0.876), respectively. The combination model was the indicator with the best AUC to predict mortality in 28 days (all p < 0.05). Patients with the percentage of PD-L1+ NK cells above the cutoff point 5.58% (hazard ratio (HR) 10.128 (1.372–74.772), p = 0.001), and the combination model prediction possibility above 0.1241 (HR 13.730 (3.241–58.158), p < 0.001) were the indexes that had greater discriminative capacity to predict 28 days mortality. Conclusions The percentage of PD-L1+ NK cells at admission serves as a novel prognostic biomarker for predicting mortality and contributes to improve the predictive capacity of SOFA score in patients with sepsis.
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spelling doaj.art-b3b924d5148a4031beabc5317e7fcf3d2022-12-22T02:43:16ZengBMCCritical Care1364-85352020-10-0124111010.1186/s13054-020-03329-zIncreased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort studyWenqiang Jiang0Xusheng Li1Miaoyun Wen2Xiaoyu Liu3Kangrong Wang4Qiaosheng Wang5Ya Li6Maohua Zhou7Mengting Liu8Bei Hu9Hongke Zeng10Department of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Critical Care Medicine, The First Affiliated Hospital, University of South ChinaDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDivision of Laboratory, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesAbstract Background Natural killer (NK) cells play a major role in immune tolerance after sepsis, and the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system mediates evasion of host immunity. The correlation between PD-L1 levels in NK cells and the prognosis of patients with sepsis, however, has not been elucidated. Thus, it was hypothesized that PD-L1 in NK cells could be a novel biomarker of the mortality for sepsis patients. Methods A prospective, observational, cohort study in a general intensive care unit had earlier enrolled patients according to the sepsis-3 criteria, and peripheral blood samples were collected within 24 h post-recruitment. The expression of four co-signaling molecules (PD-1, CD28, PD-L1, and CD86) in NK cells was assayed, and the sequential organ failure assessment (SOFA) scores were recorded on day 1. Patients were followed up until 28 days. Multivariate regression analysis assessed the independent risk factors for 28-day mortality. The association between biomarkers and 28-day mortality was assessed by Cox regression survival analysis. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results A total of 269 patients were recruited, and 114 patients were finally included for final analysis. Of these, 30 (26.3%) patients died during 28 days. The percentage of PD-L1+ NK cells (OR 1.022; 95% CI 1.002–1.043) and SOFA scores (OR 1.247; 95% CI 1.092–1.424) were independent risk factors for 28-day mortality. The AUC of the percentage of PD-L1+ NK cells, SOFA scores, and their combination model were 0.655 (0.559–0.742), 0.727 (0.635–0.807) and 0.808 (0.723–0.876), respectively. The combination model was the indicator with the best AUC to predict mortality in 28 days (all p < 0.05). Patients with the percentage of PD-L1+ NK cells above the cutoff point 5.58% (hazard ratio (HR) 10.128 (1.372–74.772), p = 0.001), and the combination model prediction possibility above 0.1241 (HR 13.730 (3.241–58.158), p < 0.001) were the indexes that had greater discriminative capacity to predict 28 days mortality. Conclusions The percentage of PD-L1+ NK cells at admission serves as a novel prognostic biomarker for predicting mortality and contributes to improve the predictive capacity of SOFA score in patients with sepsis.http://link.springer.com/article/10.1186/s13054-020-03329-zSepsisNK cellsPD-L1BiomarkerMortalityPrognosis
spellingShingle Wenqiang Jiang
Xusheng Li
Miaoyun Wen
Xiaoyu Liu
Kangrong Wang
Qiaosheng Wang
Ya Li
Maohua Zhou
Mengting Liu
Bei Hu
Hongke Zeng
Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study
Critical Care
Sepsis
NK cells
PD-L1
Biomarker
Mortality
Prognosis
title Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study
title_full Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study
title_fullStr Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study
title_full_unstemmed Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study
title_short Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study
title_sort increased percentage of pd l1 natural killer cells predicts poor prognosis in sepsis patients a prospective observational cohort study
topic Sepsis
NK cells
PD-L1
Biomarker
Mortality
Prognosis
url http://link.springer.com/article/10.1186/s13054-020-03329-z
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