Evangelos Bellos, Dilys Santillo, Pierre Vantourout, Heather R Jackson, Amedine Duret, Henry Hearn, Yoann Seeleuthner, Estelle Talouarn, Stephanie Hodeib, Harsita Patel, Oliver Powell, Sophya Yeoh, Sobia Mustafa, Dominic Habgood-Coote, Samuel Nichols, Leire Estramiana Elorrieta, Giselle D'Souza, Victoria J Wright, Diego Estrada-Rivadeneyra, Adriana H Tremoulet, Kirsten B Dummer, Stejara A Netea, Antonio Condino-Neto, Yu Lung Lau, Esmeralda Núñez Cuadros, Julie Toubiana, Marisol Holanda Pena, Frédéric Rieux-Laucat, Charles-Edouard Luyt, Filomeen Haerynck, Jean Louis Mège, Samya Chakravorty, Elie Haddad, Marie-Paule Morin, Özge Metin Akcan, Sevgi Keles, Melike Emiroglu, Gulsum Alkan, Sadiye Kübra Tüter Öz, Sefika Elmas Bozdemir, Guillaume Morelle, Alla Volokha, Yasemin Kendir-Demirkol, Betul Sözeri, Taner Coskuner, Aysun Yahsi, Belgin Gulhan, Saliha Kanik-Yuksek, Gulsum Iclal Bayhan, Aslinur Ozkaya-Parlakay, Osman Yesilbas, Nevin Hatipoglu, Tayfun Ozcelik, Alexandre Belot, Emilie Chopin, Vincent Barlogis, Esra Sevketoglu, Emin Menentoglu, Zeynep Gokce Gayretli Aydin, Marketa Bloomfield, Suzan A AlKhater, Cyril Cyrus, Yuriy Stepanovskiy, Anastasiia Bondarenko, Fatma Nur Öz, Meltem Polat, Jiří Fremuth, Jan Lebl, Amyrath Geraldo, Emmanuelle Jouanguy, Michael J Carter, Paul Wellman, Mark Peters, Rebeca Pérez de Diego, Lindsey Ann Edwards, Christopher Chiu, Mahdad Noursadeghi, Alexandre Bolze, Chisato Shimizu, Myrsini Kaforou, Melissa Shea Hamilton, Jethro A Herberg, Erica G Schmitt, Agusti Rodriguez-Palmero, Aurora Pujol, Jihoon Kim, Aurélie Cobat, Laurent Abel, Shen-Ying Zhang, Jean-Laurent Casanova, Taco W Kuijpers, Jane C Burns, Michael Levin, Adrian C Hayday, Vanessa Sancho-Shimizu
{"title":"Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).","authors":"Evangelos Bellos, Dilys Santillo, Pierre Vantourout, Heather R Jackson, Amedine Duret, Henry Hearn, Yoann Seeleuthner, Estelle Talouarn, Stephanie Hodeib, Harsita Patel, Oliver Powell, Sophya Yeoh, Sobia Mustafa, Dominic Habgood-Coote, Samuel Nichols, Leire Estramiana Elorrieta, Giselle D'Souza, Victoria J Wright, Diego Estrada-Rivadeneyra, Adriana H Tremoulet, Kirsten B Dummer, Stejara A Netea, Antonio Condino-Neto, Yu Lung Lau, Esmeralda Núñez Cuadros, Julie Toubiana, Marisol Holanda Pena, Frédéric Rieux-Laucat, Charles-Edouard Luyt, Filomeen Haerynck, Jean Louis Mège, Samya Chakravorty, Elie Haddad, Marie-Paule Morin, Özge Metin Akcan, Sevgi Keles, Melike Emiroglu, Gulsum Alkan, Sadiye Kübra Tüter Öz, Sefika Elmas Bozdemir, Guillaume Morelle, Alla Volokha, Yasemin Kendir-Demirkol, Betul Sözeri, Taner Coskuner, Aysun Yahsi, Belgin Gulhan, Saliha Kanik-Yuksek, Gulsum Iclal Bayhan, Aslinur Ozkaya-Parlakay, Osman Yesilbas, Nevin Hatipoglu, Tayfun Ozcelik, Alexandre Belot, Emilie Chopin, Vincent Barlogis, Esra Sevketoglu, Emin Menentoglu, Zeynep Gokce Gayretli Aydin, Marketa Bloomfield, Suzan A AlKhater, Cyril Cyrus, Yuriy Stepanovskiy, Anastasiia Bondarenko, Fatma Nur Öz, Meltem Polat, Jiří Fremuth, Jan Lebl, Amyrath Geraldo, Emmanuelle Jouanguy, Michael J Carter, Paul Wellman, Mark Peters, Rebeca Pérez de Diego, Lindsey Ann Edwards, Christopher Chiu, Mahdad Noursadeghi, Alexandre Bolze, Chisato Shimizu, Myrsini Kaforou, Melissa Shea Hamilton, Jethro A Herberg, Erica G Schmitt, Agusti Rodriguez-Palmero, Aurora Pujol, Jihoon Kim, Aurélie Cobat, Laurent Abel, Shen-Ying Zhang, Jean-Laurent Casanova, Taco W Kuijpers, Jane C Burns, Michael Levin, Adrian C Hayday, Vanessa Sancho-Shimizu","doi":"10.1084/jem.20240699","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 12","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586762/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1084/jem.20240699","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions.
Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
