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Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C)
E. Bellos, D. Santillo, P. Vantourout, HR. Jackson, A. Duret, H. Hearn, Y. Seeleuthner, E. Talouarn, S. Hodeib, H. Patel, O. Powell, S. Yeoh, S. Mustafa, D. Habgood-Coote, S. Nichols, L. Estramiana Elorrieta, G. D'Souza, VJ. Wright, D....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
MR/S032304/1
UK Research and Innovation
Francis Crick Institute
UL1 TR001866
NCATS NIH HHS - United States
108439/Z/15/Z
Wellcome Trust - United Kingdom
FC001003
Cancer Research UK - United Kingdom
Imagine Institute
101057100
H2020 UNDINE HORIZON-HLTH-2021-DISEASE-04
JPB Foundation
Fisher Center for Alzheimer's Research Foundation
202131-32-33
Fundació La Marató de TV3
EC-GA no. 279185
European Union's Seventh Framework Programme
R33HD105590
National Institute for Child Heath and Development
EQU201903007798
French Foundation for Medical Research
PA0873
NIHR Imperial Biomedical Research Centre
Rockefeller University
EQU202103012670
Fondation pour la recherche Medicale
Imperial College London
58READIE
Medical Research Council - United Kingdom
Meyer Foundation
FC001003
Arthritis Research UK - United Kingdom
ES/M001660/1
Economic and Social Research Council
Generalitat de Catalunya
Battersea & Bowery Advisory Group
R01AI163029
NIH HHS - United States
Grandir - Fonds de solidarité pour l'enfance
848196
European Union's Horizon 2020 research and innovation
2021SGR00899
Agencia de Gestión de Ayudas Universitarias y de Investigación
Institut National de la Santé et de la Recherche Médicale
R33 HD105590
NICHD NIH HHS - United States
R21 AI160576
NIAID NIH HHS - United States
French Ministry of Higher Education, Research, and Innovation
Howard Hughes Medical Institute - United States
Square Foundation
Fondation du Souffle
SCOR Corporate Foundation for Science
St. Giles Foundation
Wellcome Trust - United Kingdom
MR/N01104X/1 2018-2020
Economic and Social Research Council
General Atlantic Foundation
R01 AI163029
NIAID NIH HHS - United States
FC001003
Wellcome Trust - United Kingdom
ACCI20-759
CIBERER
ANR-10-IAHU-01
French National Research Agency
NLK
Free Medical Journals
od 1896 do Před 6 měsíci
Europe PubMed Central
od 1896 do Před 6 měsíci
Open Access Digital Library
od 1896-01-01
Open Access Digital Library
od 1896-01-01
Open Access Digital Library
od 1996-01-01
PubMed
39576310
DOI
10.1084/jem.20240699
Knihovny.cz E-zdroje
- MeSH
- butyrofiliny * genetika metabolismus MeSH
- COVID-19 * genetika komplikace imunologie virologie MeSH
- dítě MeSH
- genetická predispozice k nemoci MeSH
- heterozygot MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- SARS-CoV-2 * MeSH
- syndrom systémové zánětlivé reakce * genetika MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.
Aix Marseille University APHM Marseille France
Biocon Bristol Myers Squibb Research and Development Center Syngene Intl Ltd Bengaluru India
Bristol Myers Squibb Lawrenceville NJ USA
Catalan Institution of Research and Advanced Studies Barcelona Spain
CBC BIOTEC Biobank GHE Hospices Civils de Lyon Lyon France
Centre for Biomedical Research on Rare Diseases Instituto de Salud Carlos 3 Madrid Spain
Centre for Paediatrics and Child Health Faculty of Medicine Imperial College London London UK
CHU Sainte Justine Azrieli Research Center Montreal Canada
College of Medicine Imam Abdulrahman Bin Faisal University Dammam Saudi Arabia
Department of Biomedical Informatics University of California San Diego CA USA
Department of Immunology Institute of Biomedical Sciences University of Sao Paulo Sao Paulo Brazil
Department of Infectious Disease Imperial College London London UK
Department of Microbiology Infectious Diseases and Immunology University of Montreal Montreal Canada
Department of Molecular Biology and Genetics Bilkent University Ankara Turkey
Department of Pediatric Infectious Diseases Ankara City Hospital Ankara Turkey
Department of Pediatric Infectious Diseases Gazi University School of Medicine Ankara Turkey
Department of Pediatrics King Fahad Hospital of the University Al Khobar Saudi Arabia
Department of Pediatrics Necker Hospital for Sick Children Paris France
Department of Pediatrics University of Montreal Montreal Canada
Division of Infection and Immunity University College London London UK
Division of Pediatric Infectious Diseases Medical Faculty Necmettin Erbakan University Konya Turkey
Emory University Department of Pediatrics and Human Genetics Atlanta GA USA
Ghent Univer sity Hospital Ghent Belgium
Hospital Universitario Marqués de Valdecilla Santander Spain
Howard Hughes Medical Institute Rockefeller University New York NY USA
Imagine Institute Paris Descartes Sorbonne Université Paris Cité Paris France
Imagine Institute Université Paris Cité Paris France
Immunosurveillance Laboratory The Francis Crick Institute London UK
Intensive Care Unit AP HP Pitié Salpêtrière Hospital Paris University Paris France
La Timone Children Hospital Aix Marseille University APHM Marseille France
Neurometabolic Diseases Laboratory Bellvitge Biomedical Research Institute Barcelona Spain
Rady Children's Hospital San Diego San Diego CA USA
Section of Biomedical Informatics and Data Science Yale School of Medicine New Haven CT USA
University College London Great Ormond St Institute of Child Health London UK
Yildirim Beyazit University Ankara City Hospital Ankara Turkey
Citace poskytuje Crossref.org
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