20.500.12556/DiRROS-24493 Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C) 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. human diseases genetics Infectious diseases and host defense innate immunity and inflammation SARS-Cov-2 true false true Angleški jezik Ni določen Neznano 2025-12-02 13:35:54 2025-12-02 13:35:55 2025-12-03 03:42:20 0000-00-00 00:00:00 2024 0 0 str. 1-31 iss. 12, ǂ[article no.] ǂe920240699 Vol. 221 2024 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 616-097 1540-9538 10.1084/jem.20240699 230729475 RAZ_Bellos_Evangelos_2024.pdf RAZ_Bellos_Evangelos_2024.pdf 1 BD7782413A6C523D7186108A1A070A37 c21c26e9489239b852f5c7380ad61811a00cf8f4aa3bace300cc243e300e751d c2dafd6c-cf7b-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36501 https://rupress.org/jem/article/221/12/e920240699/277108/Heterozygous-BTNL8-variants-in-individuals-with 0 7850698c-cf7b-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36500 Univerzitetni klinični center Ljubljana 0 0 0