Evidence map›Paper›PMID 40111224›Full record

ArticleThe Journal of experimental medicine2025

Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design.

Kevin Groen, Roger Kuratli, Jannik Enkelmann, Sonja Fernbach, Pedro D Wendel-Garcia, Willy I Staiger, Marylène Lejeune, Esther Sauras-Colón, Ferran Roche-Campo, Paraskevas Filippidis and 7 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Autoantibodies neutralizing type I interferons underlie a third of cases of Chikungunya virus encephalitis or myelitis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Human antibodies against West Nile and related orthoflaviviruses.bioRxiv : the preprint server for biology · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  17. Host Responses to SARS-CoV-2 with an Emphasis on Cytokines.International journal of molecular sciences · 2026
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Kevin GroenInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0000-0001-6352-1346
Roger KuratliInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0009-0004-2917-575X
Jannik EnkelmannInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0009-0005-4958-0565
Sonja FernbachInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0000-0002-3362-3832
Pedro D Wendel-GarciaInstitute of Intensive Care Medicine, University Hospital Zurich, University of Zurich , Zurich, Switzerland.ORCID 0000-0001-7775-3279
Willy I StaigerDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID 0009-0007-9869-9292
Marylène LejeuneBiobank IISPV-Node Tortosa, Hospital Verge de la Cinta, Institut d'Investigació Sanitària Pere Virgili (IISPV) , Tortosa, Spain.ORCID 0000-0001-8441-9404
Esther Sauras-ColónClinical Studies Unit, Hospital Verge de la Cinta, Institut d'Investigació Sanitària Pere Virgili (IISPV) , Tortosa, Spain.ORCID 0000-0003-1649-938X
Ferran Roche-CampoIntensive Care Unit, Hospital Verge de la Cinta, Institut d'Investigació Sanitària Pere Virgili (IISPV), Tortosa, Spain.ORCID 0000-0002-4330-1706
Paraskevas FilippidisInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-6784-7420
Andri RauchDepartment of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID 0000-0001-5297-6062
Swiss HIV Cohort Study
Alexandra TrkolaInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0000-0003-1013-876X
Huldrych F GünthardInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0000-0002-1142-6723
Roger D KouyosInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0000-0002-9220-8348
Silvio D BruggerDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-9492-9088
Benjamin G HaleInstitute of Medical Virology, University of Zurich , Zurich, Switzerland.ORCID 0000-0002-3891-9480

Funding

Novartis Foundation for Medical-Biological Research 23A069Swiss National Science Foundation 320030-232029University of ZurichUSZ Foundation USZF270808
6 · The paper itself

Abstract

Autoantibodies neutralizing type I interferons (IFN-Is; IFNα or IFNω) exacerbate severe viral disease, but specific treatments are unavailable. With footprint profiling, we delineate two dominant IFN-I faces commonly recognized by neutralizing IFN-I autoantibody-containing plasmas from aged individuals with HIV-1 and from individuals with severe COVID-19. These faces overlap with IFN-I regions independently essential for engaging the IFNAR1/IFNAR2 heterodimer, and neutralizing plasmas efficiently block the interaction of IFN-I with both receptor subunits in vitro. In contrast, non-neutralizing autoantibody-containing plasmas limit the interaction of IFN-I with only one receptor subunit and display relatively low IFN-I-binding avidities, thus likely hindering neutralizing function. Iterative engineering of signaling-inert mutant IFN-Is (simIFN-Is) retaining dominant autoantibody targets created potent decoys that prevent IFN-I neutralization by autoantibody-containing plasmas and that restore IFN-I-mediated antiviral activity. Additionally, microparticle-coupled simIFN-Is were effective at depleting IFN-I autoantibodies from plasmas, leaving antiviral antibodies unaffected. Our study reveals mechanisms of action for IFN-I autoantibodies and demonstrates a proof-of-concept strategy to alleviate pathogenic effects.

Indexed as

Antibodies, NeutralizingAutoantibodiesInterferon Type ICOVID-19HEK293 CellsHIV-1HIV InfectionsHumansReceptor, Interferon alpha-betaSARS-CoV-2Antibodies, NeutralizingAutoantibodiesIFNAR2 protein, humanInterferon Type IReceptor, Interferon alpha-beta

Identifiers

PMID40111224
PMCPMC11924951

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.