患有严重 Powassan、Usutu 或罗斯河病毒病的患者体内的 Auto-Abs 中和 I 型 IFN。

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

机构信息

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.

Imagine Institute, Paris Cité University , Paris, France.

出版信息

J Exp Med. 2024 Dec 2;221(12). doi: 10.1084/jem.20240942. Epub 2024 Nov 1.

DOI:10.1084/jem.20240942

PMID:39485284

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11533500/

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).

摘要

虫媒病毒病是一个日益严重的全球健康问题。预先存在的中和 I 型干扰素（IFN）的自身抗体（auto-Abs）可能是西尼罗河病毒（WNV）（约 40%的患者）和蜱传脑炎（TBE，由 TBE 病毒[TBEV]引起）（约 10%）引起脑炎的基础。我们在这里报告称，这些自身抗体也可能是罕见虫媒病毒感染的严重形式的基础。在研究的单一重症 Powassan 病毒（POWV）脑炎病例、研究的三例重症 Usutu 病毒（USUV）感染病例中的两例以及研究的 24 例 Ross River 病毒（RRV）疾病中最严重的病例中，存在中和高浓度 IFN-α2、IFN-β和/或 IFN-ω的自身抗体。这些自身抗体在这三种病毒的 137 名无症状或轻度感染者中均未发现。因此，中和 I 型 IFN 的自身抗体是由蚊（WNV、USUV、RRV）或蜱（TBEV、POWV）传播给人类的黄病毒科（WNV、TBEV、POWV、USUV）或披膜病毒科（RRV）病毒引起的越来越多的严重虫媒病毒病的基础。