{"doi":"10.1084/jem.20240699","title":"Heterozygous <i>BTNL8</i> variants in individuals with multisystem inflammatory syndrome in children (MIS-C)","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.","journal":"The Journal of Experimental Medicine","year":2024,"id":439345,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1250028,"name":"David Santillo","orcid":"0009-0004-3966-4952","position":1,"is_corresponding":false},{"id":312633,"name":"Pierre Vantourout","orcid":"0000-0001-7287-5517","position":2,"is_corresponding":false},{"id":814348,"name":"Heather Jackson","orcid":"0000-0002-1054-9983","position":3,"is_corresponding":false},{"id":262985,"name":"Amédine Duret","orcid":"0000-0002-5810-2195","position":4,"is_corresponding":false},{"id":1250029,"name":"Henry J. 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