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Record W4413975172 · doi:10.1101/2025.08.31.25334556

Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts

2025· preprint· en· W4413975172 on OpenAlexafffund
Adrian Gervais, Francesca Trespidi, Alessandro Ferrari, Francesca Rovida, Astrid Marchal, Stefania Croce, Irene Cassaniti, Mattia Moratti, Jennifer L. Uhrlaub, David M. Florian, Karin Stiasny, Elisa Burdino, Micol Angelini, Lucy Bizien, Daniele Lilleri, Veronica Codullo, Tal Freund, Yael Paran, Avi Gadoth, Roni Biran, Alessandro Mancon, Camilla Lucca, Stefania Vogiatzis, Monia Pacenti, Mélodie Aubart, Marco Zecca, Patrizia Comoli, Maria Antonietta Avanzini, Jacques Fellay, Antonio Piralla, Francesca Conti, Alberto Dolci, Luisa Barzon, Valeria Ghisetti, Tiziana Lazzarotto, Danilo Cereda, Alessandro Aiuti, Emmanuelle Jouanguy, Paul Bastard, Margaret R. MacDonald, Charles M. Rice, Anne Puel, Laurent Abel, Giada Rossini, Davide Mileto, Yannick Simonin, Anna Nagy, David Hagin, Kristy O. Murray, Fausto Baldanti, Judith H. Aberle, Aurélie Cobat, Shen‐Ying Zhang, Jean-Laurent Casanova, A. Borghesi

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicCytomegalovirus and herpesvirus research
Canadian institutionsUniversity Hospital Foundation
FundersHospital for Sick ChildrenUniversità degli Studi di PaviaInstitut National de la Santé et de la Recherche MédicaleAgence Nationale de la RechercheSt. Giles Foundation
KeywordsAutoantibodyVirologyEncephalitisMedicineAutoimmune encephalitisImmunologyType (biology)BiologyAntibodyVirus

Abstract

fetched live from OpenAlex

Abstract 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, p <10 −16 ) 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, p <10 −16 ) 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. Summary In 13 cohorts of individuals with WNV infection, the risk of WNV encephalitis is increased 20 to >2,000 times by circulating auto-Abs neutralizing type I IFNs, depending on the concentration and combination of type I IFNs neutralized and patient age.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.021

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
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 head0.032
GPT teacher head0.327
Teacher spread0.295 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations1
Published2025
Admission routes2
Has abstractyes

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