Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C)
Bellos, Evangelos (Imperial College London)
Santillo, Dilys (Imperial College London)
Vantourout, Pierre (King's College London)
Jackson, Heather R. (Imperial College London)
Duret, Amedine (Imperial College London)
Hearn, Henry (Imperial College London)
Seeleuthner, Yoann (The Hospital for Sick Children)
Talouarn, Estelle (The Hospital for Sick Children)
Hodeib, Stephanie (Imperial College London)
Patel, Harsita (Imperial College London)
Powell, Oliver (Imperial College London)
Yeoh, Sophya (Imperial College London)
Mustafa, Sobia (Imperial College London)
Habgood-Coote, Dominic (Imperial College London)
Nichols, Samuel (Imperial College London)
Estremiana-Elorrieta, Leire (Imperial College London)
D'Souza, Giselle (Imperial College London)
Wright, Victoria (Imperial College London)
Estrada-Rivadeneyra, Diego (Imperial College London)
Tremoulet, Adriana (University of California San Diego)
Dummer, Kirsten (University of California San Diego)
Netea, Stejara (Universiteit van Amsterdam)
Condino-Neto, Antonio (University of Sao Paulo)
Lau, Yu Lung (The University of Hong Kong)
Nuñez Cuadros, Esmeralda (Hospital Regional Universitario de Málaga)
Toubiana, Julie
Holanda Pena, MS.
Rieux-Laucat, Frédéric
Luyt, Charles-Edouard (Necker-Enfants Malades University Hospital)
Haerynck, Filomeen (Ghent University Hospital (Gant, Bèlgica))
Mége, Jean-Louis (Aix-Marseille University)
Chakravorty, Samya (Biocon Bristol Myers Squibb Research and Development Center)
Haddad, Elie (University of Montreal)
Morin, Marie Paule (University of Montreal)
Metin Akcan, Özge (Necmettin Erbakan University)
Keles, Sevgi (Necmettin Erbakan University)
Emiroglu, Melike (Selcuk University Faculty of Medicine)
Alkan, Gülsüm (Selcuk University Faculty of Medicine)
Kübra Tüter Öz, Sadiye (Selcuk University Faculty of Medicine)
Bozdemir, Sefika Elmas (Necmettin Erbakan University)
Morelle, Guillaume (University of Paris-Saclay)
Volokha, Alla (Shupyk National Healthcare University)
Kendir-Demirkol, Yasemin (Health Sciences University)
Sözeri, Betul (University of Health Sciences)
Coskuner, Taner (University of Health Sciences)
Yahsi, Aysun (Ankara City Hospital (Turquia))
Gulhan, Belgin (Ankara City Hospital (Turquia))
Kanik-Yuksek, Saliha (Ankara City Hospital (Turquia))
Bayhan, G.I. (Ankara City Hospital (Turquia))
Ozkaya-Parlakay, Aslinur (Ankara City Hospital (Turquia))
Yesilbas, Osman (Karadeniz Technical University)
Hatipoglu, Nevil (University of Health Sciences)
Ozcelik, Tayfun (Bilkent University)
Belot, Alexandre (Hôpital Femme-Mère-Enfant, Groupement Hospitalier Est - Bâtiment "Pinel")
Chopin, Emilie (Hospices Civils de Lyon)
Barlogis, Vincent (Aix-Marseille University)
Sevketoglu, Esra (Univeristy of Health Sciences Turkiye Bakirkoy Dr. Sadi Konuk Research and Training Hospital Pediatirc Intensive Care Department)
Menentoglu, Emin (Univeristy of Health Sciences Turkiye Bakirkoy Dr. Sadi Konuk Research and Training Hospital Pediatirc Intensive Care Department)
Gayretli Aydin, Zeynep Gokce (Karadeniz Technical University)
Bloomfield, M.
AlKhater, Suzan (Department of Pediatrics. King Fahad Hospital of the University)
Cyrus, C. (Imam Abdulrahman Bin Faisal University (Dammam, Aràbia Saudí). Department of Biochemistry. College of Medicine)
Stepanovskyy, Yuriy (Department of Pediatrics. Immunology. Infectious. and Rare Diseases. International European University)
Bondarenko, A. (International European University)
Öz, F.N. (Department of Pediatric Infectious Disease. SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital)
Polat, M. (Department of Pediatric Infectious Diseases. Gazi University School of Medicine)
Fremuth, J. (Department of Pediatrics - PICU. Faculty of Medicine in Pilsen. Charles University in Prague)
Lebl, J. (Department of Pediatrics. 2nd Faculty of Medicine. Charles University in Prague and Motol University Hospital)
Geraldo, Amyrath (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Jouanguy, Emmanuelle (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Carter, M.J. (King's College London. St Thomas' Hospital)
Wellman, P. (Guy's and St Thomas' NHS Foundation Trust)
Peters, Mark (University College London Great Ormond St Institute of Child Health)
Perez de Diego, Rebeca (Instituto de Investigación Sanitaria del Hospital Universitario La Paz (Madrid))
Edwards, L.A. (King's College London. Guy's Hospital)
Chiu, C. (Imperial College London. Department of Infectious Disease)
Noursadeghi, M. (University College London)
Bolze, Alexandre (Helix)
Shimizu, C. (Rady Children's Hospital-San Diego)
Kaforou, Myrsini (Imperial College London)
Hamilton, M.S. (Imperial College London)
Herberg, Jethro A. (Imperial College London)
Schmitt, E.G. (Washington University in St. Louis)
Rodríguez-Palmero, Agustí (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pujol, Aurora 1968- (Hospital Universitari de Bellvitge)
Kim, Jihoon (Yale School of Medicine)
Cobat, Aurélie (The Rockefeller University)
Abel, Laurent (The Rockefeller University)
Zhang, Shen-Ying (The Rockefeller University)
Casanova, Jean-Laurent (Department of Pediatrics. Necker Hospital for Sick Children)
Kuijpers, T.W. (Department of Molecular Hematology. Sanquin Research and Landsteiner Laboratory at the AmsterdamUMC. Amsterdam Institute for Infection and Immunity. AmsterdamUMC. University of Amsterdam)
Burns, J.C. (Rady Children's Hospital-San Diego)
Levin, Michael (Imperial College London)
Hayday, A.C. (Francis Crick Institute)
Sancho Shimizu, Vanessa (Imperial College London)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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). BTNL8 encodes an intestinal epithelial regulator of Vγ4γδ 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 Vγ4γδ 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.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00899
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	The journal of experimental medicine, Vol. 221 Núm. 12 (february 2024) , p. e920240699, ISSN 1540-9538

DOI: 10.1084/jem.20240699
PMID: 39576310

31 p, 6.2 MB

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