TY - JOUR
T1 - Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children
AU - Lee, Danyel
AU - Le Pen, Jérémie
AU - Yatim, Ahmad
AU - Dong, Beihua
AU - Aquino, Yann
AU - Ogishi, Masato
AU - Pescarmona, Rémi
AU - Talouarn, Estelle
AU - Rinchai, Darawan
AU - Zhang, Peng
AU - Perret, Magali
AU - Liu, Zhiyong
AU - Jordan, Iolanda
AU - Bozdemir, Sefika Elmas
AU - Bayhan, Gulsum Iclal
AU - Beaufils, Camille
AU - Bizien, Lucy
AU - Bisiaux, Aurelie
AU - Lei, Weite
AU - Hasan, Milena
AU - Chen, Jie
AU - Gaughan, Christina
AU - Asthana, Abhishek
AU - Libri, Valentina
AU - Luna, Joseph M.
AU - Jaffré, Fabrice
AU - Hoffmann, H. Heinrich
AU - Michailidis, Eleftherios
AU - Moreews, Marion
AU - Seeleuthner, Yoann
AU - Bilguvar, Kaya
AU - Mane, Shrikant
AU - Flores, Carlos
AU - Zhang, Yu
AU - Arias, Andrés A.
AU - Bailey, Rasheed
AU - Schlüter, Agatha
AU - Milisavljevic, Baptiste
AU - Bigio, Benedetta
AU - Le Voyer, Tom
AU - Materna, Marie
AU - Gervais, Adrian
AU - Moncada-Velez, Marcela
AU - Pala, Francesca
AU - Lazarov, Tomi
AU - Levy, Romain
AU - Neehus, Anna Lena
AU - Rosain, Jérémie
AU - Peel, Jessica
AU - Chan, Yi-Hao
AU - Morin, Marie-Paule
AU - Pino-Ramirez, Rosa Maria
AU - Belkaya, Serkan
AU - Lorenzo, Lazaro
AU - Anton, Jordi
AU - Delafontaine, Selket
AU - Toubiana, Julie
AU - Bajolle, Fanny
AU - Fumadó, Victoria
AU - DeDiego, Marta L.
AU - Fidouh, Nadhira
AU - Rozenberg, Flore
AU - Pérez-Tur, Jordi
AU - hen, Shuibing
AU - Evans, Todd
AU - Geissmann, Frédéric
AU - Lebon, Pierre
AU - Weiss, Susan R.
AU - Bonnet, Damien
AU - Duval, Xavier
AU - Pan-Hammarström, Qiang
AU - Planas, Anna M.
AU - Meyts, Isabelle
AU - Haerynck, Filomeen
AU - Pujol, Aurora
AU - Sancho-Shimizu, Vanessa
AU - Dalgard, Clifford L.
AU - Bustamante, Jacinta
AU - Puel, Anne
AU - Boisson-Dupuis, Stéphanie
AU - Boisson, Bertrand
AU - Maniatis, Tom
AU - Zhang, Qian
AU - Bastard, Paul
AU - Notarangelo, Luigi
AU - Béziat, Vivien
AU - Perez de Diego, Rebeca
AU - Rodriguez-Gallego, Carlos
AU - Su, Helen C.
AU - Lifton, Richard P.
AU - Jouanguy, Emmanuelle
AU - Cobat, Aurélie
AU - Alsina, Laia
AU - Keles, Sevgi
AU - Haddad, Elie
AU - Abel, Laurent
AU - Belot, Alexandre
AU - Quintana-Murci, Lluis
AU - Rice, Charles M.
AU - Silverman, Robert H.
AU - Zhang, Shen-Ying
AU - Casanova, Jean-Laurent
AU - Colobran Oriol, Roger
AU - Rodriguez Palmero Seuma, Agustin
N1 - Publisher Copyright:
© 2023 American Association for the Advancement of Science. All rights reserved.
PY - 2023/2/10
Y1 - 2023/2/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85147787850&partnerID=8YFLogxK
U2 - 10.1126/science.abo3627
DO - 10.1126/science.abo3627
M3 - Article
C2 - 36538032
AN - SCOPUS:85147787850
SN - 0036-8075
VL - 379
JO - Science
JF - Science
IS - 6632
M1 - eabo3627
ER -