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

TitleInborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.
Publication TypeJournal Article
Year of Publication2022
AuthorsLee, D, Le Pen, J, Yatim, A, Dong, B, Aquino, Y, Ogishi, M, Pescarmona, R, Talouarn, E, Rinchai, D, Zhang, P, Perret, M, Liu, Z, Jordan, I, Bozdemir, SElmas, Bayhan, GIclal, Beaufils, C, Bizien, L, Bisiaux, A, Lei, W, Hasan, M, Chen, J, Gaughan, C, Asthana, A, Libri, V, Luna, JM, Jaffré, F, Hoffmann, H-H, Michailidis, E, Moreews, M, Seeleuthner, Y, Bilguvar, K, Mane, S, Flores, C, Zhang, Y, Arias, AA, Bailey, R, Schlüter, A, Milisavljevic, B, Bigio, B, Le Voyer, T, Materna, M, Gervais, A, Moncada-Velez, M, Pala, F, Lazarov, T, Levy, R, Neehus, A-L, Rosain, J, Peel, J, Chan, Y-H, Morin, M-P, Pino-Ramirez, RMaria, Belkaya, S, Lorenzo, L, Anton, J, Delafontaine, S, Toubiana, J, Bajolle, F, Fumadó, V, DeDiego, ML, Fidouh, N, Rozenberg, F, Pérez-Tur, J, Chen, S, Evans, T, Geissmann, F, Lebon, P, Weiss, SR, Bonnet, D, Duval, X, Covid, HGenetic Ef, Pan-Hammarström, Q, Planas, AM, Meyts, I, Haerynck, F, Pujol, A, Sancho-Shimizu, V, Dalgard, C, Bustamante, J, Puel, A, Boisson-Dupuis, S, Boisson, B, Maniatis, T, Zhang, Q, Bastard, P, Notarangelo, L, Béziat, V, de Diego, RPerez, Rodriguez-Gallego, C, Su, HC, Lifton, RP, Jouanguy, E, Cobat, A, Alsina, L, Keles, S, Haddad, E, Abel, L, Belot, A, Quintana-Murci, L, Rice, CM, Silverman, RH, Zhang, S-Y, Casanova, J-L
Corporate AuthorsCoV-Contact Cohort§
JournalScience
Paginationeabo3627
Date Published2022 Dec 20
ISSN1095-9203
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 dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1- but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by 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.

DOI10.1126/science.abo3627
Alternate JournalScience
PubMed ID36538032