Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema

Abstract Patients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. We aimed to investigate novel dysregulated cytokines that can be used as biomarkers for infectious pleural effusions, especially for CPPE/empy...

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Autores principales:	Chia-Yu Yang, Yu-Hsuan Kuo, Min Chen, Chih-Liang Wang, Li-Jane Shih, Yu-Ching Liu, Pei-Chun Hsueh, Yi-Hsuan Lai, Chi-Ming Chu, Chih-Ching Wu, Kuo-An Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b16fafe185748a186e52c895be8b650
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spelling	oai:doaj.org-article:9b16fafe185748a186e52c895be8b6502021-12-02T13:56:55ZPleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema10.1038/s41598-021-81053-62045-2322https://doaj.org/article/9b16fafe185748a186e52c895be8b6502021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81053-6https://doaj.org/toc/2045-2322Abstract Patients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. We aimed to investigate novel dysregulated cytokines that can be used as biomarkers for infectious pleural effusions, especially for CPPE/empyema. Expression of 40 cytokines in parapneumonic effusions (PPE) was screened in the discovery phase, involving 63 patients, using a multiplex immunobead-based assay. Six cytokines were subsequently validated by enzyme-linked immunosorbent assays (ELISAs). We then used ELISA to further evaluate the diagnostic values and cutoff values of these cytokines as potential biomarkers in an expanded group that included 200 patients with uncomplicated parapneumonic effusion (UPPE), CPPE, empyema, transudates, other exudates, and malignant pleural effusion (MPE). The pleural levels of four cytokines (MIF, MIP-3α, IL-1β, ENA-78) were highest and significantly increased in CPPE/empyema compared with those in other etiologies. According to receiver operating characteristic curve analysis, the four cytokines (MIF, MIP-3α, IL-1β, and ENA-78) had areas under the curve (AUCs) greater than 0.710 for discriminating parapneumonic pleural effusion from noninfectious pleural effusions. In a comparison of nonpurulent CPPE with UPPE, logistic regression analysis revealed that pleural fluid MIF ≥ 12 ng/ml and MIP-3α ≥ 4.3 ng/ml had the best diagnostic value; MIF also displayed the highest odds ratio of 663 for nonpurulent CPPE, with 97.5% specificity, 94.44% sensitivity, and an AUC of 0.950. In conclusion, our results show that elevated MIF and MIP-3α may be used as novel biomarkers for PPE diagnosis, particularly in patients with CPPE/empyema; the findings indicate that dysregulated cytokine expression may provide clues about the pathogenesis of pleural infection.Chia-Yu YangYu-Hsuan KuoMin ChenChih-Liang WangLi-Jane ShihYu-Ching LiuPei-Chun HsuehYi-Hsuan LaiChi-Ming ChuChih-Ching WuKuo-An WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chia-Yu Yang Yu-Hsuan Kuo Min Chen Chih-Liang Wang Li-Jane Shih Yu-Ching Liu Pei-Chun Hsueh Yi-Hsuan Lai Chi-Ming Chu Chih-Ching Wu Kuo-An Wu Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema
description	Abstract Patients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. We aimed to investigate novel dysregulated cytokines that can be used as biomarkers for infectious pleural effusions, especially for CPPE/empyema. Expression of 40 cytokines in parapneumonic effusions (PPE) was screened in the discovery phase, involving 63 patients, using a multiplex immunobead-based assay. Six cytokines were subsequently validated by enzyme-linked immunosorbent assays (ELISAs). We then used ELISA to further evaluate the diagnostic values and cutoff values of these cytokines as potential biomarkers in an expanded group that included 200 patients with uncomplicated parapneumonic effusion (UPPE), CPPE, empyema, transudates, other exudates, and malignant pleural effusion (MPE). The pleural levels of four cytokines (MIF, MIP-3α, IL-1β, ENA-78) were highest and significantly increased in CPPE/empyema compared with those in other etiologies. According to receiver operating characteristic curve analysis, the four cytokines (MIF, MIP-3α, IL-1β, and ENA-78) had areas under the curve (AUCs) greater than 0.710 for discriminating parapneumonic pleural effusion from noninfectious pleural effusions. In a comparison of nonpurulent CPPE with UPPE, logistic regression analysis revealed that pleural fluid MIF ≥ 12 ng/ml and MIP-3α ≥ 4.3 ng/ml had the best diagnostic value; MIF also displayed the highest odds ratio of 663 for nonpurulent CPPE, with 97.5% specificity, 94.44% sensitivity, and an AUC of 0.950. In conclusion, our results show that elevated MIF and MIP-3α may be used as novel biomarkers for PPE diagnosis, particularly in patients with CPPE/empyema; the findings indicate that dysregulated cytokine expression may provide clues about the pathogenesis of pleural infection.
format	article
author	Chia-Yu Yang Yu-Hsuan Kuo Min Chen Chih-Liang Wang Li-Jane Shih Yu-Ching Liu Pei-Chun Hsueh Yi-Hsuan Lai Chi-Ming Chu Chih-Ching Wu Kuo-An Wu
author_facet	Chia-Yu Yang Yu-Hsuan Kuo Min Chen Chih-Liang Wang Li-Jane Shih Yu-Ching Liu Pei-Chun Hsueh Yi-Hsuan Lai Chi-Ming Chu Chih-Ching Wu Kuo-An Wu
author_sort	Chia-Yu Yang
title	Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema
title_short	Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema
title_full	Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema
title_fullStr	Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema
title_full_unstemmed	Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema
title_sort	pleural cytokines mif and mip-3α as novel biomarkers for complicated parapneumonic effusions and empyema
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b16fafe185748a186e52c895be8b650
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Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema

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