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脓毒症中的免疫亚型:一项采用聚类方法的回顾性队列研究

Immune Subtypes in Sepsis: A Retrospective Cohort Study Utilizing Clustering Methodology.

作者信息

Zhao Jian, Dai Rushun, Zhao Yi, Tan Jiaping, Hao Di, Ren Jie, Wang Xianwen, Chen Yanqing, Peng Hu, Zhuang Yugang, Zhou Shuqin, Chen Yuanzhuo

机构信息

Department of Emergency, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China.

Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China.

出版信息

J Inflamm Res. 2024 Dec 28;17:11719-11728. doi: 10.2147/JIR.S491137. eCollection 2024.

DOI:10.2147/JIR.S491137
PMID:39749000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11693935/
Abstract

BACKGROUND

Sepsis is a heterogeneous clinical syndrome. Identifying distinct clinical phenotypes may enable more targeted therapeutic interventions and improve patient care.

OBJECTIVE

This study aims to use clustering analysis techniques to identify different immune subtypes in sepsis patients and explore their clinical relevance and prognosis.

METHODS

The study included 236 patients from the EICU at Shanghai Tenth People's Hospital, who met the Sepsis 3.0 diagnostic criteria. Blood samples were collected to measure lymphocyte subsets and cytokine levels, along with demographic and clinical data. K-means clustering analysis was used to categorize patients into three groups based on immune and inflammatory markers.

RESULTS

Three immune subtypes were identified: the high immune activation subtype (Cluster 1), characterized by high levels of CRP and WBC, high levels of T cells, NK cells, and B cells, and low levels of IL-6, IL-8, and IL-10; the moderate immune activation subtype (Cluster 2), characterized by moderate levels of CRP, WBC, T cells, NK cells, B cells, IL-6, IL-8, and IL-10; and the high inflammation and immune suppression subtype (Cluster 3), characterized by very high levels of IL-6, IL-8, and IL-10, low levels of T cells, NK cells, and B cells, and relatively lower CRP levels. Patients in Cluster 3 had a significantly increased 28-day mortality risk compared to those in Cluster 1 (HR = 21.65, 95% CI: 7.46-62.87, p < 0.001). Kaplan-Meier survival curves showed the lowest survival rates for Cluster 3 and the highest for Cluster 1, with the differences among the three groups being highly statistically significant (p < 0.0001).

CONCLUSION

This study identified three immune subtypes of sepsis that are significantly associated with clinical outcomes. These findings provide evidence for personalized treatment strategies to improve patient outcomes.

摘要

背景

脓毒症是一种异质性临床综合征。识别不同的临床表型可能有助于采取更具针对性的治疗干预措施并改善患者护理。

目的

本研究旨在使用聚类分析技术识别脓毒症患者的不同免疫亚型,并探讨其临床相关性和预后。

方法

该研究纳入了上海第十人民医院急诊重症监护病房(EICU)符合脓毒症3.0诊断标准的236例患者。采集血样以检测淋巴细胞亚群和细胞因子水平,同时收集人口统计学和临床数据。采用K均值聚类分析根据免疫和炎症标志物将患者分为三组。

结果

识别出三种免疫亚型:高免疫激活亚型(聚类1),其特征为CRP和白细胞水平高,T细胞、自然杀伤(NK)细胞和B细胞水平高,而白细胞介素(IL)-6、IL-8和IL-10水平低;中度免疫激活亚型(聚类2),其特征为CRP、白细胞、T细胞、NK细胞、B细胞、IL-6、IL-8和IL-10水平中等;高炎症和免疫抑制亚型(聚类3),其特征为IL-6、IL-8和IL-10水平非常高,T细胞、NK细胞和B细胞水平低,且CRP水平相对较低。与聚类1中的患者相比,聚类3中的患者28天死亡风险显著增加(风险比[HR]=21.65,95%置信区间[CI]:7.46 - 62.87,p<0.001)。Kaplan-Meier生存曲线显示聚类3的生存率最低,聚类1的生存率最高,三组之间的差异具有高度统计学意义(p<0.0001)。

结论

本研究识别出与临床结局显著相关的三种脓毒症免疫亚型。这些发现为改善患者结局的个性化治疗策略提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/8af8e37e8a17/JIR-17-11719-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/9fda597a2277/JIR-17-11719-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/97032c3726fd/JIR-17-11719-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/8af8e37e8a17/JIR-17-11719-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/9fda597a2277/JIR-17-11719-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/97032c3726fd/JIR-17-11719-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24f/11693935/8af8e37e8a17/JIR-17-11719-g0003.jpg

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本文引用的文献

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Crit Care. 2024 May 28;28(1):183. doi: 10.1186/s13054-024-04964-6.
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Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators.脓毒症中的免疫抑制:生物标志物与特殊的促消退介质
Biomedicines. 2024 Jan 13;12(1):175. doi: 10.3390/biomedicines12010175.
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Intensive Care Med. 2023 Nov;49(11):1360-1369. doi: 10.1007/s00134-023-07239-w. Epub 2023 Oct 18.
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Association Between IL10 Polymorphisms and the Susceptibility to Sepsis: A Meta-Analysis.白细胞介素 10 多态性与脓毒症易感性的关联:一项荟萃分析。
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Inflammation and Cell Death of the Innate and Adaptive Immune System during Sepsis.脓毒症时固有免疫和适应性免疫系统的炎症和细胞死亡。
Biomolecules. 2021 Jul 10;11(7):1011. doi: 10.3390/biom11071011.
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