Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).
Year: 2024
Type: article
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.
Source: Figshare
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, 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, 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, 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, Effort, COVID-19 Human Genetic, DIAMONDS, EUCLIDS, Carter, Michael J, Wellman, Paul, Peters, Mark, de Diego, Rebeca Pérez, 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
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6964073885
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