Gervais Adrian, Trespidi Francesca, Ferrari Alessandro, Rovida Francesca, Marchal Astrid, Croce Stefania, Cassaniti Irene, Moratti Mattia, Uhrlaub Jennifer L, Florian David M, Stiasny Karin, Burdino Elisa, Angelini Micol, Bizien Lucy, Lilleri Daniele, Codullo Veronica, Freund Tal, Paran Yael, Gadoth Avi, Biran Roni, Mancon Alessandro, Lucca Camilla, Vogiatzis Stefania, Pacenti Monia, Aubart Mélodie, Zecca Marco, Comoli Patrizia, Avanzini Maria Antonietta, Fellay Jacques, Piralla Antonio, Conti Francesca, Dolci Alberto, Barzon Luisa, Ghisetti Valeria, Lazzarotto Tiziana, Cereda Danilo, Aiuti Alessandro, Jouanguy Emmanuelle, Bastard Paul, MacDonald Margaret R, Rice Charles M, Puel Anne, Abel Laurent, Rossini Giada, Mileto Davide, Simonin Yannick, Nagy Anna, Hagin David, Murray Kristy O, Baldanti Fausto, Aberle Judith H, Cobat Aurélie, Zhang Shen-Ying, Casanova Jean-Laurent, Borghesi Alessandro
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, EU.
Paris Cité University, Imagine Institute, Paris, France, EU.
medRxiv. 2025 Sep 4:2025.08.31.25334556. doi: 10.1101/2025.08.31.25334556.
Mosquito-borne West Nile virus (WNV) infection is a growing global health problem. About 0.5% of infected individuals develop encephalitis. We previously showed that 40% of patients in six cohorts had WNV encephalitis because of circulating auto-antibodies (auto-Abs) neutralizing type I IFNs. In seven new cohorts, we found that the prevalence of auto-Abs was highest (40% [17-44%]) in patients with encephalitis, and very low in a small sample of individuals with asymptomatic or mild infection. In the 13 European, Middle-Eastern and American cohorts available, odds ratios for WNV encephalitis in individuals with these auto-Abs relative to those without them in a large sample of the general population untested for WNV infection range from ~20 (OR=17.7; 95% CI: 13.8-22.8, <10) for auto-Abs neutralizing only 100 pg/mL IFN-α2 and/or IFN-ω to >2000 (OR=2218.4; 95% CI: 125.1-39337.7, <10) for auto-Abs neutralizing high concentrations of IFN-α2 and high or low concentrations of IFN-ω. Pre-existing autoantibodies neutralizing type I IFNs are therefore causal for WNV encephalitis in about 40% of patients.
蚊媒传播的西尼罗河病毒（WNV）感染是一个日益严重的全球健康问题。约0.5%的感染者会发展为脑炎。我们之前表明，在六个队列中，40%的患者患有WNV脑炎是由于循环自身抗体（自身抗体）中和了I型干扰素。在七个新队列中，我们发现自身抗体的患病率在脑炎患者中最高（40%[17 - 44%]），而在一小部分无症状或轻度感染的个体样本中非常低。在现有的13个欧洲、中东和美国队列中，在未检测WNV感染的大量普通人群样本中，有这些自身抗体的个体相对于没有这些自身抗体的个体患WNV脑炎的优势比范围从~20（OR = 17.7；95%CI：13.8 - 22.8，<10），对于仅中和100 pg/mL IFN-α2和/或IFN-ω的自身抗体，到>2000（OR = 2218.4；95%CI：125.1 - 39337.7，<10），对于中和高浓度IFN-α2和高或低浓度IFN-ω的自身抗体。因此，预先存在的中和I型干扰素的自身抗体是约40%患者患WNV脑炎的病因。
