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Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients

A. Gervais, A. Marchal, A. Fortova, M. Berankova, L. Krbkova, M. Pychova, J. Salat, S. Zhao, N. Kerrouche, T. Le Voyer, K. Stiasny, S. Raffl, A. Schieber Pachart, S. Fafi-Kremer, S. Gravier, DF. Robbiani, L. Abel, MR. MacDonald, CM. Rice, G....

. 2024 ; 221 (10) : . [pub] 20240924

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24018718

Grantová podpora
Strasbourg University
EQU201903007798 French Foundation for Medical Research
Rockefeller University
Meyer Foundation
European Union
RC08061819 Italian Ministry of Health
ANR-10-IAHU-01 Agence Nationale de la Recherche
08061821 San Matteo Hospital
Imagine Institute
R01 AI163029 NIAID NIH HHS - United States
LX22N-PO5103 National Institute of Virology and Bacteriology
UL1 TR001866 NCATS NIH HHS - United States
R01 AI124690 NIAID NIH HHS - United States
Battersea & Bowery Advisory Group
R01AI163029 NIH HHS - United States
Grandir - Fonds de solidarité pour l'enfance
Howard Hughes Medical Institute - United States
Square Foundation
PRI 7782 Strasbourg University Hospital
NU22-05-00659 Czech Ministry of Health
Fondation du Souffle
SCOR Corporate Foundation for Science
St. Giles Foundation
UMR_S 1109 Institut National de la Santé et de la Recherche Médicale
Bettencourt-Schueller Foundation
PHRCN-17-0382 Ministry of Health
Paris Cité University
JPB Foundation
MESRI-COVID-19 French Ministry of Higher Education, Research, and Innovation
Stavros Niarchos Foundation
Fisher Center for Alzheimer's Research Foundation

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.

CHU de Strasbourg Service des Maladies Infectieuses et Tropicales Strasbourg France

Clinical Immunology Department Assistance Publique Hôpitaux de Paris Saint Louis Hospital Paris France

Clinical Research Department Hôpitaux Civils de Colmar Colmar France

Department of Children's Infectious Diseases University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Infectious Diseases University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatrics and Neonatology F Tappeiner Hospital Merano Italy

Department of Pediatrics Necker Hospital for Sick Children AP HP Paris France

Howard Hughes Medical Institute New York NY USA

Imagine Institute Paris Cité University Paris France

Infectious Disease Unit Provincial Hospital of Bolzano Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität Bolzano Italy

Infectious Diseases Department Hôpitaux Civils Colmar France

Institut de Virologie Strasbourg University Hospital Strasbourg University INSERM Unité Mixte de Recherche S1109 Strasbourg France

Institute for Research in Biomedicine Università della Svizzera italiana Bellinzona Switzerland

Institute of Parasitology Biology Centre of the Czech Academy of Science České Budějovice Czech Republic

Laboratory of Emerging Viral Diseases Veterinary Research Institute Brno Czech Republic

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

Laboratory of Microbiology and Virology SABES ASDAA Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität Bolzano Italy

Laboratory of Virology and Infectious Disease The Rockefeller University New York NY USA

Medical University of Vienna Center for Virology Vienna Austria

Neonatal Intensive Care Unit San Matteo Research Hospital Pavia Italy

Pediatric Hematology Immunology and Rheumatology Unit Necker Hospital for Sick Children AP HP Paris France

School of Life Sciences Swiss Federal Institute of Technology Lausanne Switzerland

St Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch Rockefeller University New York NY USA

Citace poskytuje Crossref.org

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$a Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients / $c A. Gervais, A. Marchal, A. Fortova, M. Berankova, L. Krbkova, M. Pychova, J. Salat, S. Zhao, N. Kerrouche, T. Le Voyer, K. Stiasny, S. Raffl, A. Schieber Pachart, S. Fafi-Kremer, S. Gravier, DF. Robbiani, L. Abel, MR. MacDonald, CM. Rice, G. Weissmann, T. Kamal Eldin, E. Robatscher, EM. Erne, E. Pagani, A. Borghesi, A. Puel, P. Bastard, A. Velay, M. Martinot, Y. Hansmann, JH. Aberle, D. Ruzek, A. Cobat, SY. Zhang, JL. Casanova
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$a 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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