Evidence map›Paper›PMID 41697746›Full record

ArticleThe Journal of clinical investigation2026

Type I IFN-dependent FcγRIV signaling in murine monocytes promotes lethal anaphylaxis during viral infections.

Abdelrahman Elwy, Hossam Abdelrahman, Julia Specht, Gina M Ewert, Justa Friebus-Kardash, Swati Dhiman, Julia Falkenstein, Theresa Charlotte Christ, Elisa Wiebeck, Arzoo Shamoon and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

21 authors.

Abdelrahman ElwyInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Hossam AbdelrahmanInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Julia SpechtInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Gina M EwertInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Justa Friebus-KardashInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Swati DhimanInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Julia FalkensteinInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Theresa Charlotte ChristInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Elisa WiebeckInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Arzoo ShamoonDepartment of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany.
Nils B LeimkühlerDepartment of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany.
Thomas GrambergHarald zur Hausen Institute of Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Alina RussHarald zur Hausen Institute of Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Ulrich KalinkeInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Fei KuangInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Kathrin SutterInstitute for Virology and.
Manfred KopfInstitute of Molecular Health Sciences, Department of Biology, ETH Zürich, Zürich, Switzerland.
Matthias MackDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Wiebke HansenInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Falk NimmerjahnDivision of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erlangen, Germany.
Karl S LangInstitute of Immunology, University Hospital Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anaphylaxis is a life-threatening hypersensitivity reaction. Clinical observations suggest heightened susceptibility during viral infections, yet the mechanisms remain poorly defined. Here, we show that both active and passive IgG-mediated anaphylaxis were exacerbated in the setting of acute viral infection. In mice, this enhancement was driven predominantly by FcγRIV, the homolog of human FcγRIIIa. FcγRIV crosslinking induced anaphylactic symptoms selectively in infected animals, with no effect in naive conditions. Among leukocytes, inflammatory monocytes emerged as the principal drivers of this lethal reaction. Viral infection triggered a strong upregulation of FcγRIV on inflammatory monocytes, an effect absent in type I IFN receptor-deficient (Ifnar1-deficient) mice. Extending these findings, we observed increased frequencies of CD16-expressing classical monocytes in patients with acute COVID-19, and murine SARS-CoV-2 infection recapitulated this phenotype. Mechanistically, FcγRIV crosslinking during infection promoted the production of platelet-activating factor, the key mediator of mortality, in a type I IFN-dependent (IFN-I-dependent) manner. Together, these findings indicate that viral infection creates an immune milieu that heightens monocyte sensitivity to Fcγ receptor engagement, positioning these cells as major effectors of IgG-mediated hypersensitivity in the infected host. They further suggest that Fc receptor pathway modulation merits further investigation in contexts with heightened IFN-I responses, such as in systemic lupus erythematosus.

Indexed as

AnaphylaxisCOVID-19Interferon Type IMonocytesReceptors, IgGSARS-CoV-2Signal TransductionAnimalsFemaleHumansImmunoglobulin GMaleMiceMice, Inbred C57BLMice, KnockoutReceptor, Interferon alpha-betaFcgr3 protein, mouseIfnar1 protein, mouseImmunoglobulin GInterferon Type IReceptor, Interferon alpha-betaReceptors, IgGAllergyAutoimmunityCOVID-19ImmunologyInfectious diseaseInnate immunity

Identifiers

PMID41697746
PMCPMC12904709

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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.