小柯机器人

研究揭示重症COVID-19患者中保护性免疫状态的全局性缺失
2021-01-28 13:41

美国加州大学旧金山分校Matthew F. Krummel等研究人员合作揭示重症COVID-19患者中保护性免疫状态的全局性缺失。这一研究成果于2021年1月25日在线发表在国际学术期刊《自然》上。

为了解COVID-19病理的严重/轻度区别及其起源,研究人员进行了全血液单细胞分析,从而整合了所有主要细胞类型(包括嗜中性粒细胞、单核细胞、血小板、淋巴细胞和血清含量)的贡献程度。轻度COVID-19患者在每个细胞群体中均表现出协调的干扰素刺激基因(ISG)表达模式,而在重症患者中系统性地缺乏这些细胞。与轻度疾病相比,COVID-19重症患者也反常产生很高的抗SARS-CoV-2抗体滴度,并且病毒载量较低。

对重症患者血清的检查表明,它们通过参与保守的信号传导途径来减弱干扰素对细胞的反应,从而独特地产生抗体,这些抗体在功能上能够阻断疾病相关轻度ISG表达细胞的产生。严重的抗体反应使许多COVID-19患者以及其他病毒感染患者的免疫系统无法抵抗自身,因此,这项研究定义了重症患者重获病毒防御的免疫靶标。 

据悉,尽管SARS-CoV-2感染对某些患者具有多效性和全身性影响,但在许多人中的症状却较轻。

附:英文原文

Title: Global absence and targeting of protective immune states in severe COVID-19

Author: Alexis J. Combes, Tristan Courau, Nicholas F. Kuhn, Kenneth H. Hu, Arja Ray, William S. Chen, Nayvin W. Chew, Simon J. Cleary, Divyashree Kushnoor, Gabriella C. Reeder, Alan Shen, Jessica Tsui, Kamir J. Hiam-Galvez, Priscila Muoz-Sandoval, Wandi S. Zhu, David S. Lee, Yang Sun, Ran You, Mlia Magnen, Lauren Rodriguez, K. W. Im, Nina K. Serwas, Aleksandra Leligdowicz, Colin R. Zamecnik, Rita P. Loudermilk, Michael R. Wilson, Chun J. Ye, Gabriela K. Fragiadakis, Mark R. Looney, Vincent Chan, Alyssa Ward, Sidney Carrillo, Michael Matthay, David J. Erle, Prescott G. Woodruff, Charles Langelier, Kirsten Kangelaris, Carolyn M. Hendrickson, Carolyn Calfee, Arjun Arkal Rao, Matthew F. Krummel

Issue&Volume: 2021-01-25

Abstract: While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients1–3, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression3 across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies that functionally block the production of the mild disease-associated ISG-expressing cells, by engaging conserved signaling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many COVID-19 patients and perhaps in other viral infections and this study defines targets for immunotherapies in severe patients to re-engage viral defense.

DOI: 10.1038/s41586-021-03234-7

Source: https://www.nature.com/articles/s41586-021-03234-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0