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解析新冠病毒感染不同症状阶段的血清N-糖组特征

Decoding serum N-Glycome signatures across COVID-19 symptomatic stages.

作者信息

Yaman Mehmet Emrah, Kayili Haci Mehmet, Avci İzzet, Aksakal Alperen, Kocak Omer Faruk, Atakay Mehmet, Salih Bekir

机构信息

Faculty of Pharmacy, Department of Analytical Chemistry, Ataturk University, Erzurum, Türkiye.

Faculty of Engineering, Department of Biomedical Engineering, Karabuk University, Karabuk, Türkiye.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Sep 1;1263:124710. doi: 10.1016/j.jchromb.2025.124710. Epub 2025 Jun 23.

DOI:10.1016/j.jchromb.2025.124710
PMID:40602089
Abstract

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations, ranging from asymptomatic cases to fatal outcomes. Although significant progress has been made in understanding SARS-CoV-2, the identification of reliable biomarkers for early risk assessment and disease severity prediction remains an unmet clinical need. In this study, we characterized the serum N-glycome profiles of a cohort comprising COVID-19 patients with mild to severe symptoms and healthy controls. After enzymatic deglycosylation, serum samples were analyzed using HILIC-FLD-QTOF-MS. In case-control comparisons, COVID-19 patients exhibited a significant decrease in oligomannose and hybrid-type glycans, along with an increase in tetra-antennary and tetra-galactosylated structures. In addition, four N-glycan structures were identified as having diagnostic potential to distinguish COVID-19 cases from healthy controls. When comparing severely symptomatic COVID-19 patients to those with mild symptoms and healthy controls, a significant increase was observed in antennary fucosylated N-glycans (SLex). Moreover, ROC analysis demonstrated that an isomer of Hex5HexNAc4Neu5Ac had strong diagnostic potential (AUC > 0.8) in distinguishing severely symptomatic COVID-19 patients from healthy controls. Our study reveals a novel association between antennary fucosylation and an isomer of Hex5HexNAc4Neu5Ac in severe COVID-19, highlighting its potential relevance for biomarker discovery.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染会引发广泛的临床表现,从无症状感染到致命后果不等。尽管在了解SARS-CoV-2方面已取得重大进展,但确定用于早期风险评估和疾病严重程度预测的可靠生物标志物仍是一项尚未满足的临床需求。在本研究中,我们对一组包括症状从轻到重的新型冠状病毒肺炎(COVID-19)患者和健康对照者的血清N-糖组谱进行了表征。经酶促去糖基化后,使用亲水相互作用色谱-荧光检测-四极杆飞行时间质谱(HILIC-FLD-QTOF-MS)对血清样本进行分析。在病例对照比较中,COVID-19患者的低聚甘露糖和杂合型聚糖显著减少,同时四天线和四半乳糖基化结构增加。此外,鉴定出四种N-聚糖结构具有区分COVID-19病例与健康对照者的诊断潜力。将有严重症状的COVID-19患者与症状较轻的患者及健康对照者进行比较时,观察到天线岩藻糖基化N-聚糖(sLex)显著增加。此外,受试者工作特征(ROC)分析表明,Hex5HexNAc4Neu5Ac的一种异构体在区分有严重症状的COVID-19患者与健康对照者方面具有很强的诊断潜力(曲线下面积>0.8)。我们的研究揭示了严重COVID-19中天线岩藻糖基化与Hex5HexNAc4Neu5Ac的一种异构体之间的新关联,突出了其在生物标志物发现方面的潜在相关性。

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