Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPLEE, DanyelPEN, Jeremie LeYATIM, AhmadDONG, BeihuaAQUINO, YannOGISHI, MasatoPESCARMONA, RemiTALOUARN, EstelleRINCHAI, DarawanZHANG, PengPERRET, MagaliRICE, Charles M.SILVERMAN, Robert H.ZHANG, Shen-YingCASANOVA, Jean-LaurentLIU, ZhiyongJORDAN, IolandaBOZDEMIR, Sefika ElmasBAYHAN, Gulsum IclalBEAUFILS, CamilleBIZIEN, LucyBISIAUX, AurelieLEI, WeiteHASAN, MilenaCHEN, JieGAUGHAN, ChristinaASTHANA, AbhishekLIBRI, ValentinaLUNA, Joseph M.JAFFRE, FabriceHOFFMANN, H. HeinrichMICHAILIDIS, EleftheriosMOREEWS, MarionSEELEUTHNER, YoannBILGUVAR, KayaMANE, ShrikantFLORES, CarlosZHANG, YuARIAS, Andres A.BAILEY, RasheedSCHLUTER, AgathaMILISAVLJEVIC, BaptisteBIGIO, BenedettaVOYER, Tom LeMATERNA, MarieGERVAIS, AdrianMONCADA-VELEZ, MarcelaPALA, FrancescaLAZAROV, TomiLEVY, RomainNEEHUS, Anna-LenaROSAIN, JeremiePEEL, JessicaCHAN, Yi-HaoMORIN, Marie-PaulePINO-RAMIREZ, Rosa MariaBELKAYA, SerkanLORENZO, LazaroANTON, JordiDELAFONTAINE, SelketTOUBIANA, JulieBAJOLLE, FannyFUMADO, VictoriaDEDIEGO, Marta L.FIDOUH, NadhiraROZENBERG, FlorePEREZ-TUR, JordiCHEN, ShuibingEVANS, ToddGEISSMANN, FredericLEBON, PierreWEISS, Susan R.BONNET, DamienDUVAL, XavierPAN-HAMMARSTROM, QiangPLANAS, Anna M.MEYTS, IsabelleHAERYNCK, FilomeenPUJOL, AuroraSANCHO-SHIMIZU, VanessaDALGARD, Clifford L.BUSTAMANTE, JacintaPUEL, AnneBOISSON-DUPUIS, StephanieBOISSON, BertrandMANIATIS, TomZHANG, QianBASTARD, PaulNOTARANGELO, LuigiBEZIAT, VivienDIEGO, Rebeca Perez deRODRIGUEZ-GALLEGO, CarlosSU, Helen C.LIFTON, Richard P.JOUANGUY, EmmanuelleCOBAT, AurelieALSINA, LaiaKELES, SevgiHADDAD, ElieABEL, LaurentBELOT, AlexandreQUINTANA-MURCI, Lluis2024-04-052024-04-052023SCIENCE, v.379, n.6632, p.554-+, 20230036-8075https://observatorio.fm.usp.br/handle/OPI/58952Multisystem 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.engrestrictedAccess2',5'-oligoadenylate synthetaseoligoadenylate synthetase2-5a-dependent rnaseprotein-synthesisl pathwayactivationexpressioncleavagediseaseinhibitorarticleCopyright AMER ASSOC ADVANCEMENT SCIENCE10.1126/science.abo3627Multidisciplinary Sciences1095-9203