School of Immunology & Microbial Sciences, Kings College, London, UK.
Guy's and St Thomas' NHS Foundation Trust, London, SE17EH, UK.
Intensive Care Med. 2018 Nov;44(11):1836-1848. doi: 10.1007/s00134-018-5389-0. Epub 2018 Oct 5.
Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).
In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).
Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.
From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.
NCT02188992.
目前缺乏可靠的生物标志物来预测疑似急性感染患者的后续败血症。在因疑似急性感染就诊于急诊科（ED）的患者中，我们旨在评估 47 种白细胞生物标志物作为败血症预测因子（在 ED 就诊后 24 小时和/或 72 小时时序性器官衰竭评估评分≥2）的可靠性和区分能力。
在四个 ED 和重症监护病房（ICU）进行的多中心队列研究中，我们对标准化流式细胞术白细胞生物标志物测量进行了评估，并将疑似急性感染患者（队列 1）与两个比较队列进行了比较：已确诊败血症的 ICU 患者（队列 2）和无感染或全身炎症但需要住院治疗的 ED 患者（队列 3）。
在 2014 年 1 月至 2016 年 2 月期间，我们分别招募了队列 1、2 和 3 的 272、59 和 75 名患者。在 47 种白细胞生物标志物中，有 14 种不可靠，17 种不能区分这三个队列。对队列 1 内预测败血症进行了判别分析，涉及 8 种中性粒细胞（分化抗原（CD）CD15；CD24；CD35；CD64；CD312；CD11b；CD274；CD279）、7 种单核细胞（CD35；CD64；CD312；CD11b；HLA-DR；CD274；CD279）和一种 CD8 T 淋巴细胞生物标志物（CD279）。单独来看，只有更高的中性粒细胞 CD279 [比值比（OR）1.78（95%置信区间 1.23-2.57）；P=0.002]、更高的单核细胞 CD279 [1.32（1.03-1.70）；P=0.03]和更低的单核细胞 HLA-DR [0.73（0.55-0.97）；P=0.03]表达与随后的败血症有关。通过逻辑回归，最佳生物标志物组合是增加中性粒细胞 CD24 和中性粒细胞 CD279，以及降低单核细胞 HLA-DR 表达，但没有组合具有临床相关的预测有效性。
在疑似急性感染的 ED 患者中，从大量白细胞生物标志物中筛选出了免疫抑制生物标志物与随后的败血症相关。
NCT02188992。
