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血浆蛋白质组学揭示 SARS-CoV-2 感染后的新型免疫特征和生物标志物。

Plasma Proteomics Unveil Novel Immune Signatures and Biomarkers upon SARS-CoV-2 Infection.

机构信息

Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, 80-307 Gdańsk, Pomerania, Poland.

Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90220 Oulu, North Ostrobothnia, Finland.

出版信息

Int J Mol Sci. 2023 Mar 27;24(7):6276. doi: 10.3390/ijms24076276.

Abstract

Several elements have an impact on COVID-19, including comorbidities, age and sex. To determine the protein profile changes in peripheral blood caused by a SARS-CoV-2 infection, a proximity extension assay was used to quantify 1387 proteins in plasma samples among 28 Finnish patients with COVID-19 with and without comorbidities and their controls. Key immune signatures, including CD4 and CD28, were changed in patients with comorbidities. Importantly, several unreported elevated proteins in patients with COVID-19, such as RBP2 and BST2, which show anti-microbial activity, along with proteins involved in extracellular matrix remodeling, including MATN2 and COL6A3, were identified. RNF41 was downregulated in patients compared to healthy controls. Our study demonstrates that SARS-CoV-2 infection causes distinct plasma protein changes in the presence of comorbidities despite the interpatient heterogeneity, and several novel potential biomarkers associated with a SARS-CoV-2 infection alone and in the presence of comorbidities were identified. Protein changes linked to the generation of SARS-CoV-2-specific antibodies, long-term effects and potential association with post-COVID-19 condition were revealed. Further study to characterize the identified plasma protein changes from larger cohorts with more diverse ethnicities of patients with COVID-19 combined with functional studies will facilitate the identification of novel diagnostic, prognostic biomarkers and potential therapeutic targets for patients with COVID-19.

摘要

有几个因素会影响 COVID-19,包括合并症、年龄和性别。为了确定 SARS-CoV-2 感染引起的外周血中蛋白质谱的变化,我们使用邻近延伸分析(proximity extension assay)定量分析了 28 名芬兰 COVID-19 患者(有或无合并症)及其对照者的血浆样本中的 1387 种蛋白质。在有合并症的患者中,关键的免疫特征,包括 CD4 和 CD28,发生了变化。重要的是,在 COVID-19 患者中发现了一些未报道的升高的蛋白质,如具有抗微生物活性的 RBP2 和 BST2,以及参与细胞外基质重塑的蛋白质,包括 MATN2 和 COL6A3。与健康对照组相比,RNF41 在患者中下调。我们的研究表明,尽管存在个体间的异质性,但 SARS-CoV-2 感染会导致有合并症的患者出现明显的血浆蛋白变化,并且确定了一些与 SARS-CoV-2 感染单独存在和有合并症存在相关的新的潜在生物标志物。与 SARS-CoV-2 特异性抗体产生、长期效应和与 COVID-19 后状况的潜在关联相关的蛋白质变化也被揭示出来。进一步的研究将通过更大的、具有更多样化 COVID-19 患者种族的队列来对所识别的血浆蛋白变化进行特征分析,并结合功能研究,这将有助于确定 COVID-19 患者的新的诊断、预后生物标志物和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a4a/10093853/046366bc7268/ijms-24-06276-g001.jpg

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