| Title: |
Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C) |
| Authors: |
Bellos, Evangelos; Santillo, Dilys; Vantourout, Pierre; Jackson, Heather, R; Duret, Amedine; Hearn, Henry; Seeleuthner, Yoann; Talouarn, Estelle; Hodeib, Stephanie; Patel, Harsita; Powell, Oliver; Yeoh, Sophya; Mustafa, Sobia; Habgood-Coote, Dominic; Nichols, Samuel; Estramiana Elorrieta, Leire; D’souza, Giselle; Wright, Victoria, J; Estrada-Rivadeneyra, Diego; Tremoulet, Adriana, H; Dummer, Kirsten, B; Netea, Stejara, A; Condino-Neto, Antonio; Lau, Yu Lung; Núñez Cuadros, Esmeralda; Toubiana, Julie; Holanda Pena, Marisol; Rieux-Laucat, Frédéric; Luyt, Charles-Edouard; Haerynck, Filomeen; Mège, Jean Louis; Chakravorty, Samya; Haddad, Elie; Morin, Marie-Paule; Metin Akcan, Özge; Keles, Sevgi; Emiroglu, Melike; Alkan, Gulsum; Tüter Öz, Sadiye Kübra; Elmas Bozdemir, Sefika; Morelle, Guillaume; Volokha, Alla; Kendir-Demirkol, Yasemin; Sözeri, Betul; Coskuner, Taner; Yahsi, Aysun; Gulhan, Belgin; Kanik-Yuksek, Saliha; Bayhan, Gulsum Iclal; Ozkaya-Parlakay, Aslinur; Yesilbas, Osman; Hatipoglu, Nevin; Ozcelik, Tayfun; Belot, Alexandre; Chopin, Emilie; Barlogis, Vincent; Sevketoglu, Esra; Menentoglu, Emin; Gayretli Aydin, Zeynep Gokce; Bloomfield, Marketa; Alkhater, Suzan, A; Cyrus, Cyril; Stepanovskiy, Yuriy; Bondarenko, Anastasiia; Öz, Fatma Nur; Polat, Meltem; Fremuth, Jiří; Lebl, Jan; Geraldo, Amyrath; Jouanguy, Emmanuelle; Aiuti, Alessandro; Alsina, Laia; Andreakos, Evangelos; de Andrés Martín, Ana; Biggs, Catherine, M; Borghesi, Alessandro; Bousfiha, Amed Aziz; Blazquez-Gamero, Daniel; Brodin, Petter; Casari, Giorgio; Fellay, Jacques; Flores, Carlos; Gorochov, Guy; Erdeniz, Emine Hafize; Hammarström, Lennart; Garcia, Yolanda Jordan; Karbuz, Adem; Klocperk, Adam; Lapuente-Suanzes, Paloma; Lau, Yu-Lung; Leung, Cheng; Mansouri, Davood; Mogensen, Trine, H; Ng, Lisa F.P.; Novelli, Antonio; Novelli, Giuseppe; Okamoto, Keisuke; Okada, Satoshi; Pan-Hammarström, Qiang; Pesole, Graziano; Renia, Laurent; Rodriguez-Gallego, Carlos; Sediva, Anna; Shahrooei, Mohammad; Soler-Palacin, Pere; Spaan, András, N; Tanir, Gonul; Tayoun, Ahmad Abou; Temel, Şehime, G; Vinh, Donald, C; Cunnington, Aubrey; Herberg, Jethro, A; Kaforou, Myrsini; Broderick, Claire; Channon-Wells, Samuel; Cooray, Samantha; De, Tisham; d'Souza, Giselle; Elorrieta, Leire Estramia; Galassini, Rachel; Hamilton, Shea; Kavangh, James; Keren, Ila; Marjaneh, Mahdi Moradi; Menikou, Stephanie; Nijman, Ruud; Pennisi, Ivana; Reid, Ruth; Shah, Priyen; Vito, Ortensia; Whittaker, Elizabeth; Wilson, Clare; Womersley, Rebecca; Abdulla, Ami; Darnell, Sarah; Georgiou, Pantelis; Manzano, Jesus-Rodriguez; Moser, Nicolas; Carter, Michael, J; Tibby, Shane; Cohen, Jonathan; Davis, Francesca; Kenny, Julia; Wellman, Paul; White, Marie; Fish, Matthew; Jennings, Aislinn; Shankar-Hari, Manu; Fidler, Katy; Agranoff, Dan; Richmond, Vivien; Seal, Mathhew; Faust, Saul; Owen, Dan; Ensom, Ruth; Mckay, Sarah; Shaji, Mariya; Schranz, Rachel; Rughni, Prita; Anpanthar, Amutha; Liebeschuetz, Susan; Riddell, Anna; Divakaran, Divya; Han, Louise; Khalid, Nosheen; Malcolm, Ivone Lancoma; Schofield, Jessica; Simagan, Teresa; Peters, Mark; Bamford, Alasdair; O'Neill, Lauran; Pathan, Nazima; Daubney, Esther; White, Deborah; Heightman, Melissa; Eisen, Sarah; Segal, Terry; Wellings, Lucy; Drysdale, Simon, B; Branch, Nicole; Hamzah, Lisa; Jarman, Heather; Nyirenda, Maggie; Capozzi, Lisa; Gardiner, Emma; Moots, Robert; Nasher, Magda; Hanson, Anita; Linforth, Michelle; O'Riordan, Sean; Ellis, Don; Deep, Akash; Caro, Ivan; Shackley, Fiona; Bellini, Arianna; Gormley, Stuart; Neshat, Samira; Scholefield, Barnaby; Robbins, Ceri; Winmill, Helen; Paulus, Stéphane, C; Pollard, Andrew, J; Anthony, Mark; Hopton, Sarah; Miller, Danielle; Oliver, Zoe; Beer, Sally; Ward, Bryony; Shrestha, Shrija; Gurung, Meeru; Amatya, Puja; Pokhrel, Bhishma; Bijukchhe, Sanjeev Man; Gautam, Madhav Chandra; Kelly, Sarah; O'Reilly, Peter; Shrestha, Sonu; Martinón-Torres, Federico; Salas, Antonio; Álvez González, Fernando; Gómez, Sonia Ares; Bello, Xabier; García, Mirian Ben; Caamaño Viña, Fernando; Carnota, Sandra; Curras-Tuala, María José; Dacosta Urbieta, Ana; Suárez, Carlos Durán; Vidal, Isabel Ferreiros; Vicente, Luisa García; Gómez-Carballa, Alberto; Rial, Jose Gómez; Iglesias, Pilar Leboráns; Mallah, Narmeen; Martinón-Torres, Nazareth; Martinón, José María; Mosquera Pérez Sánchez, Belén; Pardo-Seco, Jacobo; Pischedda, Sara; Vázquez, Sara Rey; Calle, Irene Rivero; Rodríguez-Tenreiro, Carmen; Redondo-Collazo, Lorenzo; Fernández, Sonia Serén; Iglesias, Marisol Vilas; Carrol, Enitan, D; Cocklin, Elizabeth; Beckley, Rebecca; Bracken, Abbey; Evans, Ceri; Khanijau, Aakash; Lenihan, Rebecca; Lewis-Burke, Nadia; Newall, Karen; Romaine, Sam; Whitbread, Jennifer; Tsolia, Maria; Eleftheriou, Irini; Spyridis, Nikos; Tambouratzi, Maria; Maritsi, Despoina; Marmarinos, Antonios; Xagorari, Marietta; Panagiota, Lourida; Aggelos, Pefanis; Karoli, Akinosoglou; Charalambos, Gogos; Markos, Maragos; Michalis, Voulgarelis; Ioan, Stergiou; Emonts, Marieke; Lim, Emma; Isaacs, John; Bell, Kathryn; Crulley, Stephen; Fabian, Daniel; Thomson, Evelyn; Wallia, Diane; Miller, Caroline; Bell, Ashley; van der Velden, Fabian J.S.; Shenton, Geoff; Price, Ashley; Treloar, Owen; Thomas, Daisy; Rojo, Pablo; Epalza, Cristina; Villaverde, Serena; Márquez, Sonia; Gijón, Manuel; Machín, Fátima; Cabello, Laura; Hernández, Irene; Gutiérrez, Lourdes; Manzanares, Ángela; Kuijpers, Taco, W; van de Kuip, Martijn; van Furth, Marceline; van den Berg, Merlijn; Biesbroek, Giske; Verkuil, Floris; van der Zee, Carlijn; Pajkrt, Dasja; van Hensbroek, Michael Boele; Schonenberg, Dieneke; Gruppen, Mariken; Nagelkerke, Sietse; Jansen, Machiel, H; Goetschalckx, Ines; Romani, Lorenza; de Luca, Maia; Chiurchiù, Sara; Tripiciano, Costanza; Mercadante, Stefania; Vermont, Clementien, L; Moll, Henriëtte, A; Borensztajn, Dorine, M; Hagedoorn, Nienke, N; Tan, Chantal; Zachariasse, Joany; Dik, W.; Shen, Ching-Fen; Zavadska, Dace; Laivacuma, Sniedze; Rudzate, Aleksandra; Stoldere, Diana; Barzdi, Arta; Barzdi, Elza; Madelane, Monta; Gravele, Dagne; Svilz, Dace; Basmaci, Romain; Lachaume, Noémie; Bories, Pauline; Tkhayat, Rajaben; Chériaux, Laura; Davoust, Juraté; Ong, Kim-Thanh; Cotillon, Marie; de Groc, Thibault; Le, Sébastien; Vergnault, Nathalie; Sée, Hélène; Cohen, Laure; de Tugny, Alice; Danekova, Nevena; Mommert-Tripon, Marine; Brengel-Pesce, Karen; Pokorn, Marko; Kolnik, Mojca; Avčin, Tadej; Avramoska, Tanja; Bahovec, Natalija; Bogovič, Petra; Kitanovski, Lidija; Nahtigal, Mirijam; Papst, Lea; Plankar Srovin, Tina; Strle, Franc; Vincek, Katarina; van der Flier, Michiel; Tissing, Wim J.E.; Wösten-van Asperen, Roelie, M; Vastert, Sebastiaan, J; Vijlbrief, Daniel, C; Bont, Louis, J; Beudeker, Coco, R; Agyeman, Philipp; Schlapbach, Luregn; Aebi, Christoph; Usman, Mariama; Schlüchter, Stefanie; Wyss, Verena; Schöbi, Nina; Zimmermann, Elisa; Meier, Marion; Weber, Kathrin; Fink, Colin; Voice, Marie; Calvo-Bado, Leo; Steele, Michael; Holden, Jennifer; Taylor, Andrew; Calvez, Ronan; Davies, Catherine; Evans, Benjamin; Stevens, Jake; Matthews, Peter; Billing, Kyle; Zenz, Werner; Binder, Alexander; Kohlmaier, Benno; Kohlfürst, Daniela, S; Schweintzger, Nina, A; Zurl, Christoph; Hösele, Susanne; Leitner, Manuel; Pölz, Lena; Rusu, Alexandra; Rajic, Glorija; Stoiser, Bianca; Strempfl, Martina; Sagmeister, Manfred, G; Bauchinger, Sebastian; Benesch, Martin; Ceolotto, Astrid; Eber, Ernst; Gallistl, Siegfried; Haidl, Harald; Hauer, Almuthe; Hude, Christa; Kapper, Andreas; Keldorfer, Markus; Löffler, Sabine; Niedrist, Tobias; Pilch, Heidemarie; Pfleger, Andreas; Pfurtscheller, Klaus; Rödl, Siegfried; Skrabl-Baumgartner, Andrea; Strenger, Volker; Wallner, Elmar; Tauchert, Maike, K; Yeung, Shunmay; Dewez, Manuel; Bath, David; Fitchett, Elizabeth; Cresswell, Fiona; Usuf, Effua; Bojang, Kalifa; Roca, Anna; Sarr, Isatou; Saidykhan, Momodou; Ndure, Ebrahim; von Both, Ulrich; Kolberg, Laura; Schmied, Patricia; Mavridi, Ioanna; Alba-Alejandre, Irene; Haas, Nikolaus; Maier, Esther; Juranek, Sabrina; Feuchtinger, Tobias; Danhauser, Katharina; Griese, Matthias; Kappler, Matthias; Lurz, Eberhard; Schroepf, Sebastian; Hoffmann, Florian; Reiter, Karl; Schoen, Carola; Giannoni, Eric; Stocker, Martin; Posfay-Barbe, Klara, M; Heininger, Ulrich; Bernhard-Stirnemann, Sara; Niederer-Loher, Anita; Kahlert, Christian; Talucci, Giancarlo; Relly, Christa; Berger, Christoph; Riedel, Thomas; Madrigal, Pedro; Fexova, Silvie; Levin, Michael; Coin, Lachlan; Hourmat, Bernardo; Hoggart, Clive; Sancho-Shimizu, Vanessa; Abdulla, Amina; Agapow, Paul; Bartlett, Maeve; Eleftherohorinou, Hariklia; Inwald, David; Mashbat, Meg; Nadel, Simon; Rahman, Rahmeen; Shailes, Hannah; Thakker, Clare; Bokhandi, Sumit; Power, Sue; Barham, Heather; Ridout, Jenna; Thurston, Sarah; Patel, Sanjay; Mccorkell, Jenni; Davies, Patrick; Crate, Lindsey; Navarra, Helen; Carter, Stephanie; Ramaiah, Raghu; Patel, Rekha; Tuffrey, Catherine; Gribbin, Andrew; Mccready, Sharon; Hardy, Katie; Standing, Fran; O'Neill, Lauren; Abelake, Eugenia; Nsirim, Eniola; Willis, Louise; Young, Zoe; Royad, Collin; White, Sonia; Fortune, Peter-Marc; Hudnott, Phil; González, Fernando Álvez; Barral-Arca, Ruth; Cebey-López, Miriam; García, Natalia; Beiroa, Andrea Grela; Grande, Antonio Justicia; Leboráns Iglesias, Pilar; Martínez Santos, Alba Elena; Martinón Sánchez, José María; Morillo Gutiérrez, Beatriz; Mosquera Pérez, Belén; Obando Pacheco, Pablo; Rivero-Calle, Irene; del Sol Porto Silva, María; Vega, Ana; Trillo, Lucía Vilanova; Reyes, Susana Beatriz; León, María Cruz León; Mingorance, Álvaro Navarro; Barrios, Xavier Gabaldó; Vergara, Eider Oñate; Torre, Andrés Concha; Vivanco, Ana; Fernández, Reyes; Sánchez, Francisco Giménez; Forte, Miguel Sánchez; Contreras, Jesus Ruiz; Palacios, Alba; Ibarrondo, Cristina Epalza; Cooke, Elizabeth Fernández; Navarro, Marisa; Álvarez, Cristina Álvarez; Lozano, María José; Carreras, Eduardo; Sanagustín, Sonia Brió; Neth, Olaf; del Carmen Martínez Padilla, Maria; Tato, Luis Manuel Prieto; Guillén, Sara; Silveira, Laura Fernández; Moreno, David; de Groot, Ronald; van Furth, A. Marceline Tutu; Boeddha, Navin, P; Driessen, Gertjan J.A.; Hazelzet, Jan; Sanders, Elisabeth A.M.; van de Beek, Diederik; van der Ende, Arie; Philipsen, Ria H.L.A.; Adeel, Abdul O.A.; Breukels, Mijke, A; Brinkman, Danielle M.C.; de Korte, Carla C.M.M.; de Vries, Esther; de Waal, Wouter, J; Dekkers, Roel; Dings-Lammertink, Anouk; Doedens, Rienus, A; Donker, Albertine, E; Dousma, Mieke; Faber, Tina, E; Gerrits, Gerardus P.J.M.; Gerver, Jan A.M.; Heidema, Jojanneke; Homan-van der Veen, Jenneke; Jacobs, Monique A.M.; Jansen, Nicolaas J.G.; Kawczynski, Pawel; Klucovska, Kristine; Kneyber, Martin C.J.; Koopman-Keemink, Yvonne; Langenhorst, Veerle, J; Leusink, José; Loza, Bettina, F; Merth, Istvan, T; Miedema, Carien, J; Neeleman, Chris; Noordzij, Jeroen, G; Obihara, Charles, C; van Overbeek - van Gils, A. Lindy T.; Poortman, Geriska, H; Potgieter, Stephanus, T; Potjewijd, Joke; Rosias, Phillippe P.R.; Sprong, Tom; ten Tussher, Gavin, W; Thio, Boony, J; Tramper-Stranders, Gerdien, A; van Deuren, Marcel; van der Meer, Henny; van Kuppevelt, Andre J.M.; van Wermeskerken, Anne-Marie; Verwijs, Wim, A; Wolfs, Tom F.W.; Hasters, Paul; Baer, Walter; Frederick, Hannah; Jennings, Rebecca; Johnston, Joanne; Kenwright, Rhian; Pinnock, Elli; Agbeko, Rachel; Anderson, Suzanne; Secka, Fatou; Kebbeh, Ngange; Sey, Gibbi; Cole, Fatoumata; Thomas, Gilleh; Antonio, Martin; Baumgart, Hinrich; Baumgartner, Markus; Behrends, Uta; Biebl, Ariane; Birnbacher, Robert; Blanke, Jan-Gerd; Boelke, Carsten; Breuling, Kai; Brunner, Jürgen; Buller, Maria; Dahlem, Peter; Dietrich, Beate; Elias, Johannes; Emhofer, Josef; Etschmaier, Rosa; Farr, Sebastian; Girtler, Ylenia; Grigorow, Irina; Heimann, Konrad; Ihm, Ulrike; Jaros, Zdenek; Kalhoff, Hermann; Kaulfersch, Wilhelm; Kemen, Christoph; Klocker, Nina; Köster, Bernhard; Komini, Eleni; Kramer, Lydia; Neubert, Antje; Ortner, Daniel; Pescollderungg, Lydia; Ristic, Goran; Sellner, Andrea; Sonnleitner, Astrid; Sperl, Matthias; Stelzl, Wolfgang; Till, Holger; Trobisch, Andreas; Vierzig, Anne; Vogel, Ulrich; Weingarten, Christina; Welke, Stefanie; Wimmer, Andreas; Wintergerst, Uwe; Wüller, Daniel; Zaunschirm, Andrew; Ziuraite, Ieva; Žukovskaja, Veslava; Hibberd, Martin, L; Davila, Sonia; Delany, Isabel; Pérez de Diego, Rebeca; Edwards, Lindsey Ann; Chiu, Christopher; Noursadeghi, Mahdad; Bolze, Alexandre; Shimizu, Chisato; Hamilton, Melissa Shea; Schmitt, Erica, G; Rodriguez-Palmero, Agusti; Pujol, Aurora; Kim, Jihoon; Cobat, Aurélie; Abel, Laurent; Zhang, Shen-Ying; Casanova, Jean-Laurent; Burns, Jane, C; Hayday, Adrian, C |
| Contributors: |
Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020); ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020); ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018); ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021); ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021); European Project: 101057100,HORIZON-HLTH-2021-DISEASE-04,HORIZON-HLTH-2021-DISEASE-04,UNDINE(2022) |
| Source: |
ISSN: 0022-1007. |
| Publisher Information: |
CCSD; Rockefeller University Press |
| Publication Year: |
2024 |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/grantAgreement//101057100/EU/The human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection: Towards personalised medicine/UNDINE |
| DOI: |
10.1084/jem.20240699 |
| Availability: |
https://hal.science/hal-04816209; https://hal.science/hal-04816209v1/document; https://hal.science/hal-04816209v1/file/jem_20240699.pdf; https://doi.org/10.1084/jem.20240699 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.77686E6C |
| Database: |
BASE |