The Journal of experimental medicine · 2024

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

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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, COVID-19 Human Genetic Effort, DIAMONDS, EUCLIDS, Carter Michael J, Wellman Paul, Peters Mark, Pérez de Diego Rebeca, 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

Аннотация

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.

Предметные рубрики MeSH

Humans COVID-19 Child Systemic Inflammatory Response Syndrome Male Female Butyrophilins SARS-CoV-2 Child, Preschool Heterozygote Adolescent Genetic Predisposition to Disease Infant

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

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Аннотация

Предметные рубрики MeSH