| Title: | Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C) |
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| Authors: | ID Bellos, Evangelos (Author)
ID Santillo, Dilys (Author)
ID Vantourout, Pierre (Author)
ID Jackson, Heather R. (Author)
ID Duret, Amedine (Author)
ID Hearn, Henry (Author)
ID Seeleuthner, Yoann (Author)
ID Talouarn, Estelle (Author)
ID Hodeib, Stephanie (Author)
ID Patel, Harsita (Author)
ID Pokorn, Marko (Research coworker)
ID Kolnik, Mojca (Research coworker)
ID Avčin, Tadej (Author)
ID Avramoska, Tanja (Research coworker)
ID Bahovec, Natalija (Research coworker)
ID Bogovič, Petra (Research coworker)
ID Kitanovski, Lidija (Research coworker)
ID Nahtigal Klevišar, Mirijam (Research coworker)
ID Papst, Lea (Research coworker)
ID Plankar Srovin, Tina (Research coworker)
ID Strle, Franc (Research coworker)
ID Vincek, Katarina (Author), et al. |
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| Files: |  PDF - Presentation file, download (6,23 MB)
MD5: BD7782413A6C523D7186108A1A070A37
 URL - Source URL, visit https://rupress.org/jem/article/221/12/e920240699/277108/Heterozygous-BTNL8-variants-in-individuals-with
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| 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. |
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| Keywords: | human diseases genetics, Infectious diseases and host defense, innate immunity and inflammation, SARS-Cov-2 |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2024 |
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| Number of pages: | str. 1-31 |
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| Numbering: | Vol. 221, iss. 12, ǂ[article no.] ǂe920240699 |
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| PID: | 20.500.12556/DiRROS-24493  |
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| UDC: | 616-097 |
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| ISSN on article: | 1540-9538 |
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| DOI: | 10.1084/jem.20240699 |
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| COBISS.SI-ID: | 230729475 |
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| Note: |
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| Publication date in DiRROS: | 02.12.2025 |
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| Views: | 189 |
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| Downloads: | 98 |
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