{"doi":"10.1126/science.abo3627","title":"Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children","abstract":"Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.","journal":"Science","year":2022,"id":232760,"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":168,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104161,"name":"Jérémie Le Pen","orcid":"0000-0001-7025-9526","position":1,"is_corresponding":false},{"id":844005,"name":"Ahmad Yatim","orcid":"0000-0002-4859-4085","position":2,"is_corresponding":false},{"id":494763,"name":"Beihua Dong","orcid":null,"position":3,"is_corresponding":false},{"id":844006,"name":"Yann Aquino","orcid":"0000-0001-7669-4721","position":4,"is_corresponding":false},{"id":104463,"name":"Masato Ogishi","orcid":"0000-0003-2421-7389","position":5,"is_corresponding":false},{"id":844007,"name":"Rémi Pescarmona","orcid":"0000-0002-7218-3294","position":6,"is_corresponding":false},{"id":617475,"name":"Estelle Talouarn","orcid":"0000-0002-5016-0446","position":7,"is_corresponding":false},{"id":646404,"name":"Darawan Rinchai","orcid":"0000-0001-8851-7730","position":8,"is_corresponding":false},{"id":104484,"name":"Peng Zhang","orcid":"0000-0002-6129-567X","position":9,"is_corresponding":false},{"id":844008,"name":"Magali Perret","orcid":"0000-0002-9215-5186","position":10,"is_corresponding":false},{"id":104460,"name":"Zhiyong Liu","orcid":"0000-0001-6473-348X","position":11,"is_corresponding":false},{"id":84174,"name":"Iolanda Jordán","orcid":"0000-0002-2041-4425","position":12,"is_corresponding":false},{"id":628185,"name":"Şefika Elmas Bozdemir","orcid":"0000-0003-1058-0320","position":13,"is_corresponding":false},{"id":628186,"name":"Gülsüm İclal Bayhan","orcid":"0000-0002-1423-4348","position":14,"is_corresponding":false},{"id":844009,"name":"Camille Beaufils","orcid":"0000-0002-8630-3509","position":15,"is_corresponding":false},{"id":104153,"name":"Lucy Bizien","orcid":"0000-0001-9163-9122","position":16,"is_corresponding":false},{"id":844010,"name":"Aurélie Bisiaux","orcid":"0000-0002-2447-3393","position":17,"is_corresponding":false},{"id":628217,"name":"Wei‐Te Lei","orcid":"0000-0003-1677-8901","position":18,"is_corresponding":false},{"id":844011,"name":"Milena Hasan","orcid":"0000-0002-0879-7099","position":19,"is_corresponding":false},{"id":839707,"name":"Jie Chen","orcid":"0000-0001-8113-3515","position":20,"is_corresponding":false},{"id":493818,"name":"Christina Gaughan","orcid":"0000-0002-0869-9026","position":21,"is_corresponding":false},{"id":737515,"name":"Abhishek Asthana","orcid":"0000-0002-5429-6199","position":22,"is_corresponding":false},{"id":844012,"name":"Valentina Libri","orcid":"0000-0002-2080-1089","position":23,"is_corresponding":false},{"id":228341,"name":"Joseph M. 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