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PD-1/PD-L1和IL-7在淋巴细胞动态变化及脓毒症进展中的作用:一项针对危重症患者的生物标志物研究

The Role of PD-1/PD-L1 and IL-7 in Lymphocyte Dynamics and Sepsis Progression: A Biomarker Study in Critically Ill Patients.

作者信息

Coman Oana, Grigorescu Bianca-Liana, Huțanu Adina, Bacârea Anca, Văsieșiu Anca Meda, Fodor Raluca Ștefania, Petrișor Marius, Azamfirei Leonard

机构信息

Department of Simulation Applied in Medicine, University of Medicine, Pharmacy, Science and Technology "George Emil Palade", 540142 Targu Mures, Romania.

Department of Anaesthesiology and Intensive Care, University of Medicine, Pharmacy, Science and Technology "George Emil Palade", 540142 Targu Mures, Romania.

出版信息

Int J Mol Sci. 2024 Nov 24;25(23):12612. doi: 10.3390/ijms252312612.

DOI:10.3390/ijms252312612
PMID:39684323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11641135/
Abstract

Sepsis pathophysiology involves a dysregulated immune response to infection, excessive inflammation, and immune paralysis. This study explores the relationships between cell death biomarkers (serum-soluble levels of programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and interleukin-7 (IL-7)) and the percentages of various lymphocyte subsets in relation to the severity and progression of sepsis. This prospective, observational study included 87 critically ill patients. We monitored parameters on days 1 (sepsis was diagnosed according to the Sepsis-3 Consensus) and 5. We established an IL-7 cutoff value of 1.94 pg/mL by comparing levels between a healthy control group and patients with sepsis ( < 0.0001). Lymphopenia was observed in all patients, with negative correlations between helper T lymphocytes and cytotoxic and B lymphocytes, and positive correlations involving cytotoxic lymphocytes across all groups. We found correlations between PD-1/PD-L1 and lymphocyte subsets. IL-7 showed a statistical correlation with PD-1 in non-survivors. Assessing lymphocyte levels shows potential as a biomarker for evaluating the progression of sepsis. Monitoring IL-7 levels could help assess survival, as low levels are associated with higher mortality risk. Monitoring IL-7 levels could help assess survival, as low levels are associated with higher mortality risk. Elevated PD-1/PD-L1 expression impairs costimulatory signalling, reducing T cell responses and lymphopenia, which increases the risk of nosocomial infections.

摘要

脓毒症的病理生理学涉及对感染的免疫反应失调、过度炎症反应和免疫麻痹。本研究探讨细胞死亡生物标志物(程序性细胞死亡蛋白1(PD-1)、程序性死亡配体1(PD-L1)和白细胞介素-7(IL-7)的血清可溶性水平)与脓毒症严重程度和进展相关的各种淋巴细胞亚群百分比之间的关系。这项前瞻性观察性研究纳入了87例危重症患者。我们在第1天(根据脓毒症-3共识诊断脓毒症)和第5天监测各项参数。通过比较健康对照组和脓毒症患者之间的水平(<0.0001),我们确定IL-7的临界值为1.94 pg/mL。所有患者均观察到淋巴细胞减少,辅助性T淋巴细胞与细胞毒性淋巴细胞和B淋巴细胞之间呈负相关,所有组中细胞毒性淋巴细胞之间呈正相关。我们发现PD-1/PD-L1与淋巴细胞亚群之间存在相关性。在非存活者中,IL-7与PD-1呈统计学相关性。评估淋巴细胞水平显示出作为评估脓毒症进展生物标志物的潜力。监测IL-7水平有助于评估生存情况,因为低水平与更高的死亡风险相关。监测IL-7水平有助于评估生存情况,因为低水平与更高的死亡风险相关。PD-1/PD-L1表达升高会损害共刺激信号传导,降低T细胞反应并导致淋巴细胞减少,从而增加医院感染的风险。

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本文引用的文献

1
The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis.程序性细胞死亡蛋白 1/程序性死亡配体 1(PD-1/PD-L1)轴在脓毒症诱导的细胞凋亡中的作用。
Medicina (Kaunas). 2024 Jul 19;60(7):1174. doi: 10.3390/medicina60071174.
2
Expression pattern of serum interleukin-7 in elderly septic patients and its prognostic value for predicting short-term mortality.老年脓毒症患者血清白细胞介素-7的表达模式及其对预测短期死亡率的预后价值。
Cytokine. 2024 Aug;180:156664. doi: 10.1016/j.cyto.2024.156664. Epub 2024 May 24.
3
Immune profile of patients‑a new approach in management of sepsis and septic shock?
患者的免疫特征——脓毒症和脓毒性休克管理的新方法?
Exp Ther Med. 2024 Mar 15;27(5):203. doi: 10.3892/etm.2024.12489. eCollection 2024 May.
4
The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways.靶向 PD-1:PD-L1 通路通过免疫刺激和抗炎途径治疗脓毒症的意义。
Front Immunol. 2023 Dec 13;14:1323797. doi: 10.3389/fimmu.2023.1323797. eCollection 2023.
5
Immunomodulation with IL-7 and IL-15 in HIV-1 infection.HIV-1感染中白细胞介素-7和白细胞介素-15的免疫调节作用
J Virus Erad. 2023 Sep 5;9(3):100347. doi: 10.1016/j.jve.2023.100347. eCollection 2023 Sep.
6
Interleukin-7 and interleukin-15 as prognostic biomarkers in sepsis and septic shock: Correlation with inflammatory markers and mortality.白细胞介素-7 和白细胞介素-15 作为脓毒症和脓毒性休克的预后生物标志物:与炎症标志物和死亡率的相关性。
Cytokine. 2023 Sep;169:156277. doi: 10.1016/j.cyto.2023.156277. Epub 2023 Jun 20.
7
Regulatory role of the programmed cell death 1 signaling pathway in sepsis induced immunosuppression.程序性细胞死亡 1 信号通路在脓毒症诱导免疫抑制中的调节作用。
Front Immunol. 2023 May 24;14:1183542. doi: 10.3389/fimmu.2023.1183542. eCollection 2023.
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Role of regulation of PD-1 and PD-L1 expression in sepsis.PD-1 和 PD-L1 表达调控在脓毒症中的作用。
Front Immunol. 2023 Mar 9;14:1029438. doi: 10.3389/fimmu.2023.1029438. eCollection 2023.
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Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial.静脉注射白细胞介素-7逆转感染性休克患者淋巴细胞减少症:一项双盲、随机、安慰剂对照试验。
Ann Intensive Care. 2023 Mar 12;13(1):17. doi: 10.1186/s13613-023-01109-w.
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Intensive Care Med. 2023 Apr;49(4):462-464. doi: 10.1007/s00134-023-07009-8. Epub 2023 Mar 3.