C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?

Melissa A. Hausburg , Jason S. Williams , Kaysie L. Banton , Charles W. Mains , Michael Roshon , David Bar-Or
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引用次数: 2

Abstract

From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.

C1酯酶抑制剂介导的COVID-19免疫抑制:是敌是友?
从无症状到严重,COVID-19的病原体SARS-CoV-2可引起不同的疾病严重程度。此外,了解对SARS-CoV-2的先天和适应性免疫反应是必要的,因为Omicron等变异会对适应性抗体中和产生负面影响。严重的COVID-19在一定程度上与补体和因子XII(接触系统激活的启动者)的异常激活有关。矛盾的是,一种抑制补体激活和FXIIa三种已知途径的蛋白,C1酯酶抑制剂(C1- inh),在COVID-19患者血浆中增加,并与疾病严重程度相关。本文综述了C1-INH在先天和适应性免疫反应调控中的作用。此外,我们分析了其他病原体和SARS病毒对C1-INH和编码C1-INH基因SERPING1的调控,并提出病毒蛋白结合C1-INH抑制其在重症COVID-19中的功能。最后,我们回顾了目前外源性C1-INH治疗COVID-19患者的临床试验和已发表的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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