中和III型干扰素的自身抗体在2019年严重冠状病毒肺炎患者中不常见。

IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-05-29 DOI:10.1089/jir.2023.0003
Martti Vanker, Karita Särekannu, Arnaud Fekkar, Sofie Eg Jørgensen, Liis Haljasmägi, Anne Kallaste, Kalle Kisand, Margus Lember, Pärt Peterson, Madhvi Menon, Tracy Hussell, Sean Knight, James Moore-Stanley, Paul Bastard, Shen-Ying Zhang, Trine H Mogensen, Quentin Philippot, Qian Zhang, Anne Puel, Jean-Laurent Casanova, Kai Kisand
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引用次数: 0

摘要

中和I型干扰素(IFN)的自身抗体(AABs)是2019年(新冠肺炎)重症冠状病毒肺炎约15%病例的基础。自身免疫对III型IFN的影响尚未探索。我们纳入了1002名新冠肺炎患者(50%患有严重疾病)和1489名未感染严重急性呼吸系统综合征冠状病毒2型的患者的样本。我们研究了AABs对IFNλ和IFNα的流行率和中和能力。应用基于萤光素酶的免疫沉淀法,使用合并的IFNα(亚型1、2、8和21)或合并的IFN-λ1-IFNλ3作为抗原,然后进行基于报告细胞的中和测定。在严重急性呼吸系统综合征冠状病毒2型初始队列中,IFNλAABs比靶向IFNα2的AABs更常见(8.5%),并且与年龄较大有关。在新冠肺炎队列中,对IFNλ的自身反应与严重疾病无关[比值比(OR)0.84;95%置信区间(CI)0.40-1.73],与IFNα不同(OR 4.88;95%CI 2.40-11.06;P
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Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

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来源期刊
CiteScore
3.80
自引率
0.00%
发文量
78
审稿时长
2.2 months
期刊介绍: Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.
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