单核细胞HLA-DR在感染性休克患者中的表达:来自20年1023例真实世界队列的见解

IF 21.2 1区 医学 Q1 CRITICAL CARE MEDICINE
Guillaume Monneret, Thomas Lafon, Morgane Gossez, Bruno Evrard, Maxime Bodinier, Thomas Rimmelé, Laurent Argaud, Martin Cour, Arnaud Friggeri, Alain Lepape, Bernard Allaouchiche, Anne-Claire Lukaszewicz, Fabienne Venet
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引用次数: 0

摘要

目的:脓毒症患者同时出现高炎症和免疫抑制,后者导致ICU获得性感染,延长ICU住院时间,增加死亡率。随着免疫刺激疗法进入临床试验,有效的分层是识别最严重免疫功能障碍患者的关键。单核细胞HLA-DR表达(mHLA-DR)已成为脓毒症诱导的免疫抑制最可靠和可操作的生物标志物。方法:我们对1023例脓毒性休克患者进行了一项真实世界的20年队列研究,在ICU入院第一周通过标准化流式细胞术测量mHLA-DR。主要结局包括第28天和第90天的死亡率和icu获得性感染。结果:缓慢mHLA-DR (< 8000 AB/C,已在II期试验中使用的阈值)与死亡率和icu获得性感染增加显著相关。这种关联适用于静态和动态测量、多变量分析、Kaplan-Meier生存曲线和轨迹聚类(K-means)。结论:这项大型现实世界研究证实,mHLA-DR是一种强大的富集生物标志物,可用于识别免疫抑制程度最高的感染性休克患者的不良结局风险较高。重要的是,时间过程分析表明,早期免疫下调可能代表一种生理适应,而延迟和持续的免疫抑制与更糟糕的结果相关。早期单一时间点测量可能无法识别不太可能发生延迟性免疫抑制的患者。在ICU最初几天后跟踪mHLA-DR轨迹对于发现持续的免疫功能障碍和选择免疫刺激方法的患者至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Monocyte HLA-DR expression in septic shock patients: insights from a 20-year real-world cohort of 1023 cases

Purpose

Septic patients simultaneously experience hyperinflammation and immunosuppression, the latter driving ICU-acquired infections, prolonged stays in ICU, and increased mortality. As immunostimulant therapies enter clinical trials, effective stratification is critical to identify patients with the most profound immune dysfunction. Monocyte HLA-DR expression (mHLA-DR) has emerged as the most reliable and actionable biomarker of sepsis-induced immunosuppression.

Methods

We conducted a real-world, 20-year cohort study of 1023 septic shock patients, measuring mHLA-DR by standardized flow cytometry during the first week of ICU admission. Primary outcomes included day-28 and day-90 mortality, and ICU-acquired infections.

Results

Low mHLA-DR (< 8000 AB/C, a threshold already used in phase II trials) was significantly associated with increased mortality and ICU-acquired infections. This association held across static and dynamic measures, multivariate analyses, Kaplan–Meier survival curves, and trajectory clustering (K-means).

Conclusions

This large real-world study confirms that mHLA-DR is a robust enrichment biomarker for identifying the most immunosuppressed septic shock patients at higher risk of adverse outcomes. Importantly, time-course analysis suggests that early immune downregulation may represent a physiological adaptation, while delayed and persistent immunosuppression is associated with worse outcomes. Early single time-point measurements may fail to identify patients who are unlikely to develop delayed immunosuppression. Tracking mHLA-DR trajectories after the initial ICU days is essential for detecting persistent immune dysfunction and selecting patients in case of immunostimulant approaches.

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来源期刊
Intensive Care Medicine
Intensive Care Medicine 医学-危重病医学
CiteScore
51.50
自引率
2.80%
发文量
326
审稿时长
1 months
期刊介绍: Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.
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