Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease.

IF 12.6 1区医学 Q1 IMMUNOLOGY Journal of Experimental Medicine Pub Date : 2024-12-02 Epub Date: 2024-11-01 DOI:10.1084/jem.20240942

Adrian Gervais, Paul Bastard, Lucy Bizien, Céline Delifer, Pierre Tiberghien, Chaturaka Rodrigo, Francesca Trespidi, Micol Angelini, Giada Rossini, Tiziana Lazzarotto, Francesca Conti, Irene Cassaniti, Fausto Baldanti, Francesca Rovida, Alessandro Ferrari, Davide Mileto, Alessandro Mancon, Laurent Abel, Anne Puel, Aurélie Cobat, Charles M Rice, Dániel Cadar, Jonas Schmidt-Chanasit, Johannes F Scheid, Jacob E Lemieux, Eric S Rosenberg, Marianna Agudelo, Stuart G Tangye, Alessandro Borghesi, Guillaume André Durand, Emilie Duburcq-Gury, Braulio M Valencia, Andrew R Lloyd, Anna Nagy, Margaret M MacDonald, Yannick Simonin, Shen-Ying Zhang, Jean-Laurent Casanova

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Abstract

Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections. Auto-Abs neutralizing high concentrations of IFN-α2, IFN-β, and/or IFN-ω are present in the single case of severe Powassan virus (POWV) encephalitis studied, two of three cases of severe Usutu virus (USUV) infection studied, and the most severe of 24 cases of Ross River virus (RRV) disease studied. These auto-Abs are not found in any of the 137 individuals with silent or mild infections with these three viruses. Thus, auto-Abs neutralizing type I IFNs underlie an increasing list of severe arboviral diseases due to Flaviviridae (WNV, TBEV, POWV, USUV) or Togaviridae (RRV) viruses transmitted to humans by mosquitos (WNV, USUV, RRV) or ticks (TBEV, POWV).

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严重波瓦桑、乌苏图或罗斯河病毒病患者体内中和 I 型 IFN 的自身抗体。

虫媒病毒疾病是全球日益关注的健康问题。中和 I 型干扰素（IFNs）的原有自身抗体（auto-Abs）可能是西尼罗河病毒（WNV）脑炎（40% 的患者）和蜱传脑炎（TBE，由 TBE 病毒 [TBEV] 引起）（10%）的病因。我们在此报告，这些自身抗体也可能是较罕见的虫媒病毒感染的严重形式的基础。高浓度 IFN-α2、IFN-β 和/或 IFN-ω 中和的自身抗体存在于所研究的一例严重的波瓦桑病毒（POWV）脑炎病例、所研究的三例严重的乌苏图病毒（USUV）感染病例中的两例，以及所研究的 24 例罗斯河病毒（RRV）病例中最严重的一例。在这三种病毒的 137 例静默或轻度感染者中，没有发现这些自身抗体。因此，越来越多的严重虫媒病毒疾病是由蚊子（WNV、TBEV、POWV、USUV）或蜱虫（TBEV、POWV）传播给人类的黄病毒科（WNV）或托加病毒科（RRV）病毒引起的，这些自身抗体中和了 I 型 IFNs。

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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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.