| Title | Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Lee, 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 Authors | CoV-Contact Cohort§ |
| Journal | Science |
| Pagination | eabo3627 |
| Date Published | 2022 Dec 20 |
| ISSN | 1095-9203 |
| 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. |
| DOI | 10.1126/science.abo3627 |
| Alternate Journal | Science |
| PubMed ID | 36538032 |