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cc by (c) Lee, Danyel et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/202161

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

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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.

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LEE, Danyel, LE PEN, Jérémie, YATIM, Ahmad, DONG, Beihua, AQUINO, Yann, OGISHI, Masato, PESCARMONA, Rémi, TALOUARN, Estelle, RINCHAI, Darawan, ZHANG, Peng, PERRET, Magali, FUMADÓ, Victoria, DEDIEGO, Marta l., FIDOUH, Nadhira, ROZENBERG, Flore, PÉREZ TUR, Jordi, CHEN, Shuibing, EVANS, Todd, GEISSMANN, Frédéric, LEBON, Pierre, WEISS, Susan r., BONNET, Damien, DUVAL, Xavier, CoV-Contact Cohort, COVID Human Genetic Effort, PAN-HAMMARSTRÖM, Qiang, PLANAS OBRADORS, Anna m., MEYTS, Isabelle, HAERYNCK, Filomeen, PUJOL ONOFRE, Aurora, SANCHO SHIMIZU, Vanessa, DALGARD, Clifford l., BUSTAMANTE, Jacinta, PUEL, Anne, BOISSON-DUPUIS, Stéphanie, BOISSON, Bertrand, MANIATIS, Tom, ZHANG, Qian, BASTARD, Paul, NOTARANGELO, Luigi d., BÉZIAT, Vivien, PÉREZ DE DIEGO, Rebeca, RODRÍGUEZ GALLEGO, Carlos, SU, Helen c., LIFTON, Richard p., JOUANGUY, Emmanuelle, COBAT, Aurélie, ALSINA MANRIQUE DE LARA, Laia, KELES, Sevgi, HADDAD, Elie, CASANOVA, Jean-laurent, ABEL, Laurent, BELOT, Alexandre, ZHANG, Shen-ying, QUINTANA MURCI, Lluis, SILVERMAN, Robert h., RICE, Charles m., LIU, Zhiyong, JORDÁN GARCÍA, Iolanda, ELMAS BOZDEMIR, Sefika, BAYHAN, Gulsum iclal, BEAUFILS, Camille, BIZIEN, Lucy, BISIAUX, Aurelie, LEI, Weite, HASAN, Milena, CHEN, Jie, GAUGHAN, Christina, ASTHANA, Abhishek, LIBRI, Valentina, LUNA, Joseph m., JAFFRÉ, Fabrice, HOFFMANN, Heinrich h., MICHAILIDIS, Eleftherios, MOREEWS, Marion, SEELEUTHNER, Yoann, BILGUVAR, Kaya, MANE, Shrikant, FLORES, Carlos, ZHANG, Yu, ARIAS, Andrés a., BAILEY, Rasheed, SCHLÜTER, Agatha, MILISAVLJEVIC, Baptiste, BIGIO, Benedetta, ANTÓN LÓPEZ, Jordi, LE VOYER, Tom, MATERNA, Marie, GERVAIS, Adrian, MONCADA VELEZ, Marcela, PALA, Francesca, LAZAROV, Tomi, LEVY, Romain, NEEHUS, Anna-lena, ROSAIN, Jérémie, PEEL, Jessica, CHAN, Yi-hao, MORIN, Marie-paule, PINO RAMÍREZ, Rosa mª, BELKAYA, Serkan, LORENZO, Lazaro, DELAFONTAINE, Selket, TOUBIANA, Julie, BAJOLLE, Fanny. Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children. _Science_. 2023. Vol. 379, núm. 6632, pàgs. eabo3627. [consulta: 23 de gener de 2026]. ISSN: 0036-8075. [Disponible a: https://hdl.handle.net/2445/202161]

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