Browsing by Author "Bellos, Evangelos"

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    Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C)
    (Rockefeller University Press, 2024-11-22) 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; Elorrieta, Leire Estramiana; D’souza, Giselle; Wright, Victoria J.; Estrada-rivadeneyra, Diego; Tremoulet, Adriana H.; Dummer, Kirsten B.; Netea, Stejara A.; Condino-neto, Antonio; Lau, Yu Lung; Cuadros, Esmeralda Núñez; Toubiana, Julie; Pena, Marisol Holanda; Rieux-laucat, Frédéric; Luyt, Charles-edouard; Haerynck, Filomeen; Mège, Jean Louis; Chakravorty, Samya; Haddad, Elie; Morin, Marie-paule; Akcan, Özge Metin; Keles, Sevgi; Emiroglu, Melike; Alkan, Gulsum; Öz, Sadiye Kübra Tüter; Bozdemir, Sefika Elmas; Morelle, Guillaume; Volokha, Alla; Kendir-demirkol, Yasemin; Sözeri, Betul; Coskuner, Taner; Gulhan, Aysun Yahsi, Belgin; Kanik-yuksek, Saliha; Bayhan, Gulsum Iclal; Ozkaya-parlakay, Aslinur; Yesilbas, Osman; Hatipoglu, Nevin; Özçelik, Tayfun; Belot, Alexandre; Chopin, Emilie; Barlogis, Vincent; Sevketoglu, Esra; Menentoglu, Emin; Aydin, Zeynep Gokce Gayretli; Bloomfield, Marketa; Alkhater, Suzan A.; Cyrus, Cyril; Stepanovskiy, Yuriy; Bondarenko, Anastasiia; Öz, Fatma Nur; Polat, Meltem; Fremuth, Jiří; Lebl, Jan; Geraldo, Amyrath; Jouanguy, Emmanuelle; Carter, Michael J.; Wellman, Paul; Peters, Mark; Diego, Rebeca Pérez De; Edwards, Lindsey Ann; Chiu, Christopher; Noursadeghi, Mahdad; Bolze, Alexandre; Shimizu, Chisato; Kaforou, Myrsini; Hamilton, Melissa Shea; Herberg, Jethro A.; Schmitt, Erica G.; Rodriguez-palmero, Agusti; Pujol, Aurora; Kim, Jihoon; Cobat, Aurélie; Abel, Laurent; Zhang, Shen-ying; Casanova, Jean-laurent; Kuijpers, Taco W.; Burns, Jane C.; Levin, Michael; Hayday, Adrian C.; Sancho-shimizu, Vanessa
    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.