Evidence map›Paper›PMID 33872655›Full record

Trial reportThe Journal of allergy and clinical immunology2021

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency.

Stefano Vavassori, Janet Chou, Laura Eva Faletti, Veronika Haunerdinger, Lennart Opitz, Pascal Joset, Christopher J Fraser, Seraina Prader, Xianfei Gao, Luise A Schuch and 50 more

Registry-linked trialOpen access · bronzeAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02735824 (Genetic Study of Immunodeficiency), which is not on this map. Cited by 44 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 5% of its field
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.

NCT02735824 recruitingnot on this map

Genetic Study of Immunodeficiency: Search for New Genetic Causes for Primary Immunodeficiencies

TypeobservationalSponsorUniversity Children's Hospital, ZurichRan2016 to 2027Enrolled500ConditionsImmunologic Deficiency Syndromes, Primary Immune Deficiency (PID)ArmsSkin Biopsy, Mouth Swab or Saliva Collection, Blood Sampling
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.

  1. Pooled it
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  19. Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Rare disease genomics and precision medicine.Genomics & informatics · 2024
    Review
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

60 authors at 20 institutions in 7 countries.

Stefano VavassoriDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Janet ChouDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Laura Eva FalettiInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Veronika HaunerdingerDivision of Stem Cell Transplantation and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Lennart OpitzFunctional Genomics Center Zürich, University of Zurich, Zurich, Switzerland.
Pascal JosetInstitute of Medical Genetics, University of Zurich, Schlieren, Switzerland.
Christopher J FraserQueensland Children's Hospital, South Brisbane, Australia.
Seraina PraderDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Xianfei GaoDivision of Pediatric Pneumology, Dr. von Hauner Children's Hospital, University Hospital Munich, German Center for Lung Research (DZL), Munich, Germany.
Luise A SchuchDivision of Pediatric Pneumology, Dr. von Hauner Children's Hospital, University Hospital Munich, German Center for Lung Research (DZL), Munich, Germany.
Matias WagnerInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Julia HoefeleInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Maria Elena MaccariInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Ying ZhuNew South Wales Health Pathology Genomics, Prince of Wales Hospital, Sydney, Australia.
George ElakisNew South Wales Health Pathology Genomics, Prince of Wales Hospital, Sydney, Australia.
Michael T GabbettCentre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Maria ForstnerDivision of Pediatric Pneumology, Dr. von Hauner Children's Hospital, University Hospital Munich, German Center for Lung Research (DZL), Munich, Germany.
Heymut OmranClinic for General Pediatrics, University Hospital Münster, Münster, Germany.
Thomas KaiserClinic for General Pediatrics, University Hospital Münster, Münster, Germany.
Christina KesslerClinic for General Pediatrics, University Hospital Münster, Münster, Germany.
Heike OlbrichClinic for General Pediatrics, University Hospital Münster, Münster, Germany.
Patrick FroskDivision of Clinical Immunology and Allergy, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
Abduarahman AlmutairiDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass; Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia.
Craig D PlattDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Megan ElkinsDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Sabrina WeeksDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Tamar RubinDivision of Pediatric Clinical Immunology and Allergy, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
Raquel PlanasDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Tommaso MarchettiDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Danil KoovelyDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Verena KlämbtDivision of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Neveen A SolimanDepartment of Pediatrics, Center of Pediatric Nephrology and Transplantation, Cairo University, Cairo, Egypt.
Sandra von HardenbergDepartment of Human Genetics, Hannover Medical School, Hannover, Germany.
Christian KlemannDepartment of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
Ulrich BaumannDepartment of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
Dominic LenzDivision of Neuropediatrics and Pediatric Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Andreas Klein-FrankeDivision of Pediatric Hematology and Oncology, Cantonal Hospital Aarau, Aarau, Switzerland.
Martin SchwemmleInstitute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Michael HuberInstitute of Medical Virology, University of Zurich, Zurich, Switzerland.
Ekkehard SturmDivision of Pediatric Gastroenterology and Hepatology, University Hospital Tübingen, Tübingen, Germany.
Steffen HartleifDivision of Pediatric Gastroenterology and Hepatology, University Hospital Tübingen, Tübingen, Germany.
Karsten HäffnerDepartment of Internal Medicine IV (Nephrology), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Charlotte GimpelDepartment of Internal Medicine IV (Nephrology), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Barbara BrotschiDepartment of Pediatric and Neonatal Intensive Care, University Children's Hospital Zurich, Zurich, Switzerland.
Guido LaubeDivision of Nephrology, University Children's Hospital Zurich, Zurich, Switzerland.
Tayfun GüngörDivision of Stem Cell Transplantation and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Michael F BuckleyNew South Wales Health Pathology Genomics, Prince of Wales Hospital, Sydney, Australia.
Raimund KottkeDivision of Neuroradiology, Department of Diagnostic Imaging and Intervention, University Children's Hospital Zurich, Zurich, Switzerland.
Christian StaufnerDivision of Neuropediatrics and Pediatric Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Friedhelm HildebrandtDivision of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Simone Reu-HoferInstitute of Pathology, University of Würzburg, Würzburg, Germany.
Solange MollDepartment of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Achim WeberDepartment of Pathology and Molecular Pathology, and Institute of Molecular Cancer Research, University Hospital and University of Zurich, Zurich, Switzerland.
Hundeep KaurBiozentrum, University of Basel, Basel, Switzerland.
Stephan EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sebastian HillerBiozentrum, University of Basel, Basel, Switzerland.
Raif GehaDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass. Electronic address: raif.geha@childrens.harvard.edu.
Tony RoscioliNew South Wales Health Pathology Genomics, Prince of Wales Hospital, Sydney, Australia; Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, University of New South Wales, Sydney, Australia.
Matthias GrieseDivision of Pediatric Pneumology, Dr. von Hauner Children's Hospital, University Hospital Munich, German Center for Lung Research (DZL), Munich, Germany.
Jana Pachlopnik SchmidDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Pediatric Immunology, University of Zurich, Zurich, Switzerland. Electronic address: jana.pachlopnik@kispi.uzh.ch.
University Children's Hospital Zurich · CHBoston Children's Hospital · USUniversity of Freiburg · DEUniversity of Zurich · CHLMU Klinikum · DEUniversity Hospital Münster · DEMedizinische Hochschule Hannover · DEPrince of Wales Hospital · AUHeidelberg University · DETUM Klinikum · DEUniversity Children's Hospital Tübingen · DEUniversity of Basel · CHUniversity of Manitoba · CACairo University · EGChildren's Health Queensland Hospital and Health Service · AUKantonsspital Aarau · CHQueensland University of Technology · AUUniversity of Geneva · CHUniversity of Würzburg · DEUNSW Sydney · AU

Funding

Novel genetics, pathobiology & therapy of nephronophthisis-related ciliopathiesR01DK068306 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2004 to 2022
$6.6M
Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1R01AI139633 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI GEHA, RAIF SALIM · 2018 to 2022
$3.1M
Novel mechanisms of T cell costimulation: the role of LRRC8A in T cell activationK08AI116979 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI CHOU, JANET · 2015 to 2019
$934k
NIAID NIH HHS K08 AI116979NIAID NIH HHS R01 AI139633NIDDK NIH HHS R01 DK068306
6 · The paper itself

Abstract

backgroundRecognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known.

objectiveWe studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease.

methodsWhole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids.

resultsDeleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes.

conclusionZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.

Indexed as

Exome SequencingGenetic Predisposition to DiseaseAntigens, NeoplasmChildChild, PreschoolFemaleHumansInfantInflammationMalePrimary Immunodeficiency DiseasesVirus DiseasesAntigens, NeoplasmZNFX1 protein, humanbrain calcificationHLH-like diseaseinterstitial lung diseaseleukoencephalopathysusceptibility to viral infectionsthrombotic microangiopathytype I interferonvirally induced hepatitisZNFX1

Identifiers

PMID33872655
PMCPMC8569286
OpenAlexW3155290787

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Registered trials

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.