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白细胞介素-4、白细胞介素-10、趋化因子配体 2 和转化生长因子-β作为预测恶性疟原虫疟疾严重程度的潜在生物标志物。

IL-4, IL-10, CCL2 and TGF-β as potential biomarkers for severity in Plasmodium vivax malaria.

机构信息

Grupo Investigaciones Microbiológicas y Biomédicas de Córdoba, GIMBIC, Universidad de Córdoba, Montería, Córdoba, Colombia.

Grupo de Enfermedades Tropicales y Resistencia Bacteriana, Universidad del Sinú, Montería, Córdoba, Colombia.

出版信息

PLoS Negl Trop Dis. 2022 Sep 30;16(9):e0010798. doi: 10.1371/journal.pntd.0010798. eCollection 2022 Sep.

DOI:10.1371/journal.pntd.0010798
PMID:36178979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9555658/
Abstract

Cytokines and chemokines are immune response molecules that display diverse functions, such as inflammation and immune regulation. In Plasmodium vivax infections, the uncontrolled production of these molecules is thought to contribute to pathogenesis and has been proposed as a possible predictor for disease complications. The objective of this study was to evaluate the cytokine profile of P. vivax malaria patients with different clinical outcomes to identify possible immune biomarkers for severe P. vivax malaria. The study included patients with non-severe (n = 56), or severe (n = 50) P. vivax malaria and healthy controls (n = 50). Patient plasma concentrations of IL-4, IL-2, CXCL10, IL-1β, TNF-α, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, CXCL8 and active TGF-β1 were determined through flow cytometry. The levels of several cytokines and chemokines, CXCL10, IL-10, IL-6, IL-4, CCL2 and IFN-γ were found to be significantly higher in severe, compared to non-severe P. vivax malaria patients. Severe thrombocytopenia was positively correlated with IL-4, CXCL10, IL-6, IL-10 and IFN-γ levels, renal dysfunction was related to an increase in IL-2, IL-1β, IL-17A and IL-8, and hepatic impairment with CXCL10, MCP-1, IL-6 and IFN-γ. A Lasso regression model suggests that IL-4, IL-10, CCL2 and TGF-β might be developed as biomarkers for severity in P. vivax malaria. Severe P. vivax malaria patients present specific cytokine and chemokine profiles that are different from non-severe patients and that could potentially be developed as biomarkers for disease severity.

摘要

细胞因子和趋化因子是具有多种功能的免疫反应分子,如炎症和免疫调节。在间日疟原虫感染中,这些分子的不受控制的产生被认为有助于发病机制,并被提出作为疾病并发症的一个可能预测因子。本研究的目的是评估具有不同临床结局的间日疟原虫疟疾患者的细胞因子谱,以确定严重间日疟原虫疟疾的可能免疫生物标志物。该研究包括非严重(n=56)或严重(n=50)间日疟原虫疟疾患者和健康对照者(n=50)。通过流式细胞术测定患者血浆中 IL-4、IL-2、CXCL10、IL-1β、TNF-α、CCL2、IL-17A、IL-6、IL-10、IFN-γ、IL-12p70、CXCL8 和活性 TGF-β1 的浓度。与非严重间日疟原虫疟疾患者相比,严重间日疟原虫疟疾患者的几种细胞因子和趋化因子,如 CXCL10、IL-10、IL-6、IL-4、CCL2 和 IFN-γ的水平显著升高。严重血小板减少症与 IL-4、CXCL10、IL-6、IL-10 和 IFN-γ水平呈正相关,肾功能障碍与 IL-2、IL-1β、IL-17A 和 IL-8 增加有关,肝损伤与 CXCL10、MCP-1、IL-6 和 IFN-γ有关。套索回归模型表明,IL-4、IL-10、CCL2 和 TGF-β 可能作为间日疟原虫疟疾严重程度的生物标志物进行开发。严重的间日疟原虫疟疾患者表现出与非严重患者不同的特定细胞因子和趋化因子谱,这些特征可能作为疾病严重程度的生物标志物进行开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/22d1062328d3/pntd.0010798.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/9e9f9316aee1/pntd.0010798.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/7abbb6199316/pntd.0010798.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/420efd5d7c87/pntd.0010798.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/508e6821e382/pntd.0010798.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/22d1062328d3/pntd.0010798.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/9e9f9316aee1/pntd.0010798.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/7abbb6199316/pntd.0010798.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/420efd5d7c87/pntd.0010798.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/324c/9555658/508e6821e382/pntd.0010798.g004.jpg
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