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.
DOI: 10.5167/uzh-265039
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, et al, Collaborators, Schlapbach, Luregn J, Zimmermann, Elisa, Weber, Kathrin, Meier, Marion, et al
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6948523665
FWCI:
Cites:
Cited by:
Related to: