Adrian Gervais, Astrid Marchal, Andrea Fortova, Michaela Berankova, Lenka Krbkova, Martina Pychova, Jiri Salat, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne Schieber Pachart, Samira Fafi-Kremer, Simon Gravier, Davide F Robbiani, Laurent Abel, Margaret R MacDonald, Charles M Rice, Gaia Weissmann, Tarek Kamal Eldin, Eva Robatscher, Elke Maria Erne, Elisabetta Pagani, Alessandro Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, Martin Martinot, Yves Hansmann, Judith H Aberle, Daniel Ruzek, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent Casanova
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We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448868/pdf/","citationCount":"0","resultStr":"{\"title\":\"Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients.\",\"authors\":\"Adrian Gervais, Astrid Marchal, Andrea Fortova, Michaela Berankova, Lenka Krbkova, Martina Pychova, Jiri Salat, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne Schieber Pachart, Samira Fafi-Kremer, Simon Gravier, Davide F Robbiani, Laurent Abel, Margaret R MacDonald, Charles M Rice, Gaia Weissmann, Tarek Kamal Eldin, Eva Robatscher, Elke Maria Erne, Elisabetta Pagani, Alessandro Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, Martin Martinot, Yves Hansmann, Judith H Aberle, Daniel Ruzek, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent Casanova\",\"doi\":\"10.1084/jem.20240637\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. 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Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients.
Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.
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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.
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