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血清蛋白质组学分析揭示 2019 年冠状病毒病中免疫调节蛋白颗粒蛋白的特异性上调。

Serum Protein Profiling Reveals a Specific Upregulation of the Immunomodulatory Protein Progranulin in Coronavirus Disease 2019.

机构信息

Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

出版信息

J Infect Dis. 2021 Mar 3;223(5):775-784. doi: 10.1093/infdis/jiaa741.

Abstract

BACKGROUND

Severe courses of coronavirus disease 2019 (COVID-19) are associated with elevated levels of interleukin 6 (IL-6). However, there is a growing body of evidence pointing to a broad and more complex disorder of proinflammatory and antiviral responses with disturbed interferon signaling in COVID-19.

METHODS

In this prospective, single-center registry, we included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and patients with similar symptoms and severity of disease but negative for SARS-CoV-2 admitted to the emergency department and compared their serum protein expression profiles.

RESULTS

IL-6 abundance was similar in SARS-CoV-2-positive patients (n = 24) compared with SARS-CoV-2-negative controls (n = 61). In contrast, we observed a specific upregulation of the immunomodulatory protein progranulin (GRN). High GRN abundance was associated with adverse outcomes and increased expression of IL-6 in COVID-19.

CONCLUSIONS

The data from this registry reveal that GRN is specifically upregulated in SARS-CoV-2-positive patients while IL-6 may serve as marker for disease severity. The potential of GRN as a biomarker and a possible impact of increased GRN expression on interferon signaling, virus elimination, and virus-induced lung tissue damage in COVID-19 should be further explored.

摘要

背景

严重的 2019 年冠状病毒病(COVID-19)与白细胞介素 6(IL-6)水平升高有关。然而,越来越多的证据表明,COVID-19 存在广泛而更为复杂的促炎和抗病毒反应失调以及干扰素信号紊乱。

方法

在这项前瞻性、单中心登记研究中,我们纳入了 SARS-CoV-2 阳性患者和具有类似症状和疾病严重程度但 SARS-CoV-2 阴性的患者,并比较了他们的血清蛋白表达谱。

结果

与 SARS-CoV-2 阴性对照组(n=61)相比,SARS-CoV-2 阳性患者(n=24)的 IL-6 丰度相似。相比之下,我们观察到免疫调节蛋白颗粒蛋白前体(GRN)的特异性上调。GRN 高丰度与不良结局相关,并与 COVID-19 中 IL-6 的表达增加相关。

结论

本登记研究的数据显示,GRN 在 SARS-CoV-2 阳性患者中特异性上调,而 IL-6 可能是疾病严重程度的标志物。GRN 作为生物标志物的潜力以及 GRN 表达增加对 COVID-19 中干扰素信号、病毒清除和病毒诱导的肺组织损伤的可能影响,应进一步探讨。

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