约 40%的西尼罗河病毒脑炎患者存在中和 I 型干扰素的自身抗体。
Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients.
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.
Paris Cité University, Imagine Institute , Paris, France.
出版信息
J Exp Med. 2023 Sep 4;220(9). doi: 10.1084/jem.20230661. Epub 2023 Jun 22.
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.
蚊媒传播的西尼罗河病毒 (WNV) 感染在大多数个体中是良性的，但在 <1%的感染个体中可引起脑炎。我们表明，在来自欧盟和美国的六个独立队列中因 WNV 疾病 (WNVD) 住院的约 35%的患者携带中和 IFN-α和/或 -ω 的自身抗体。这些抗体在脑炎患者中的患病率最高（约 40%），而在无症状 WNV 感染患者中的患病率与普通人群相当。在普通人群中，与没有这些自身抗体的个体相比，这些自身抗体的个体发生 WNVD 的比值比范围从仅中和 100 pg/ml IFN-α和/或 IFN-ω 的自身抗体的 19.0（95%CI 15.0-24.0，P 值 <10-15）到中和 10ng/ml 时同时中和 IFN-α和 IFN-ω 的自身抗体的 127.4（CI 87.1-186.4，P 值 <10-15）。这些抗体在体外感染 WNV 的 Vero 细胞中阻断了 IFN-α 的保护作用。中和 IFN-α和/或 IFN-ω 的自身抗体是约 40%的 WNV 脑炎病例的基础。
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