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胸腔积液中的单核细胞亚型可揭示用于诊断结核病和恶性肿瘤的生物标志物候选物。

Monocytes subtypes from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy.

机构信息

Department of Respiratory Medicine, Key Cite of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China.

Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.

出版信息

J Clin Lab Anal. 2022 Aug;36(8):e24579. doi: 10.1002/jcla.24579. Epub 2022 Jul 12.

DOI:10.1002/jcla.24579

PMID:35819097

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9396188/

Abstract

BACKGROUND

Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion.

METHODS

Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL-1β, IL-17, IL-27, and IFN-γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real-time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions.

RESULTS

CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL-1β, IL-17, IL-27, and IFN-γ, in TPE were much higher than in other pleural effusions. Moreover, CD14 CD16 nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14 CD16 intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1-CX3CR1 axis-mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN-γ expression in TPE. Higher expression of cytokines (IL-1β, IL-17, IL-27, and IFN-γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion.

CONCLUSIONS

CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.

摘要

背景

胸腔积液是由多种呼吸系统疾病引起的一种常见临床病症，包括肺结核和恶性肿瘤。然而，快速准确地诊断结核性胸腔积液（TPE）和恶性胸腔积液（MPE）仍然具有挑战性。虽然单核细胞已被证实是结核病和恶性肿瘤中一种重要的免疫细胞，但对于单核细胞亚群在胸腔积液诊断中的作用知之甚少。

方法

分别收集 40 例 TPE 患者、40 例 MPE 患者和 24 例漏出性胸腔积液患者的胸腔积液样本和外周血样本。通过 ELISA 检测趋化因子（CCL2、CCL7 和 CX3CL1）和细胞因子（IL-1β、IL-17、IL-27 和 IFN-γ）。通过流式细胞术分析单核细胞表型。通过实时 PCR 分析不同单核细胞亚群中的趋化因子受体（CCR2 和 CX3CR1）和上述细胞因子。通过绘制受试者工作特征曲线分析，显示中间和非经典亚群在结核性和恶性胸腔积液之间的区分能力。

结果

与 MPE 和漏出性胸腔积液相比，TPE 中的 CCL7 和 CX3CL1 水平明显升高。TPE 中的细胞因子，如 IL-1β、IL-17、IL-27 和 IFN-γ，均高于其他胸腔积液。此外，TPE 中非经典亚群 CD14 CD16 的频率明显高于 MPE，而 MPE 中 CD14 CD16 中间亚群的比例升高。此外，TPE 中 CX3CL1-CX3CR1 轴介导的非经典单核细胞浸润与 TPE 中 CX3CL1 和 IFN-γ的表达有关。与其他亚群相比，非经典单核细胞中细胞因子（IL-1β、IL-17、IL-27 和 IFN-γ）的表达水平更高。此外，胸腔积液中中间和非经典单核细胞的比例具有区分结核性胸腔积液和恶性胸腔积液的能力。