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血浆中半乳糖凝集素-9 和骨桥蛋白的高水平与反映 COVID-19 肺炎严重程度的炎症标志物相关。

High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.

机构信息

Research Institute of Health and Welfare, Kibi International University, Takahashi 716-8508, Japan.

Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

出版信息

Int J Mol Sci. 2021 May 7;22(9):4978. doi: 10.3390/ijms22094978.

Abstract

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.

摘要

新型冠状病毒病 2019(COVID-19)患者的数量在全球范围内迅速增加。全长半乳糖凝集素-9(FL-Gal9)和骨桥蛋白(FL-OPN)及其截断形式(Tr-Gal9、Ud-OPN)的血浆水平是代表性的炎症生物标志物。在这里,我们测量了 94 份来自 23 名 COVID-19 感染患者(轻症组,CV)、25 名 COVID-19 合并肺炎患者(CP 组)和 14 名细菌性感染患者(ID 组)的血浆样本中的 FL-Gal9、FL-OPN、Tr-Gal9 和 Ud-OPN。与健康个体相比,CP 组中的这四种蛋白显著升高。CV 和 CP 组之间的 ROC 分析表明,C 反应蛋白具有最高的区分能力,其次是 Tr-Gal9 和铁蛋白。Spearman 相关分析表明,在 CP 患者中,Tr-Gal9 和 Ud-OPN 与肺功能、炎症、凝血障碍和肾功能的实验室标志物有显著相关性,但 FL-Gal9 和 FL-OPN 没有。接受托珠单抗治疗的 CP 患者 FL-Gal9、Tr-Gal9 和 Ud-OPN 水平降低。这表明 OPN 可被白细胞介素-6 依赖性蛋白酶切割。这些发现表明 OPN 和半乳糖凝集素-9 的切割形式可用于监测 CP 患者病理炎症的严重程度和托珠单抗的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e69/8125627/4cbeda72640d/ijms-22-04978-g001.jpg

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