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Record W4402763015 · doi:10.1084/jem.20240637

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

2024· article· en· W4402763015 on OpenAlexafffund
Adrian Gervais, Astrid Marchal, Andrea Fořtová, Michaela Beránková, Lenka Krbková, Martina Pýchová, Jiřı́ Salát, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne 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 Erne, Elisabetta Pagani, A. Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, M. Martinot, Yves Hansmann, Judith H. Aberle, Daniel Růžek, Aurélie Cobat, Shen‐Ying Zhang, Jean‐Laurent Casanova

Bibliographic record

VenueThe Journal of Experimental Medicine · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicVector-borne infectious diseases
Canadian institutionsSickKids FoundationUniversity Hospital FoundationHospital for Sick Children
FundersNational Center for Advancing Translational SciencesStavros Niarchos FoundationHospital for Sick ChildrenMinistero della SaluteFondation Bettencourt SchuellerCHIST-ERANational Institute of Allergy and Infectious DiseasesFisher Center for Alzheimer's Research FoundationAgence Nationale de la RechercheEuropean CommissionSCOR Corporate Foundation for ScienceMinistère de l'Enseignement supérieur, de la Recherche et de l'InnovationMeyer FoundationRockefeller UniversityUniversité de StrasbourgInstitut National de la Santé et de la Recherche MédicaleFondation du SouffleFondation pour la Recherche MédicaleJPB FoundationNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungInstitut des maladies génétiques ImagineHoward Hughes Medical InstituteFondazione IRCCS Policlinico San MatteoSt. Giles FoundationMinistry of Health
KeywordsEncephalitisMedicineNeutralizationPopulationTick-borne encephalitisAutoantibodyInternal medicineVirologyImmunologyVirusGastroenterologyAntibody

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.144
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.300
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations37
Published2024
Admission routes2
Has abstractyes

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