Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children Journal Article
| 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.; Elmas Bozdemir, S.; Bayhan, G. I.; Beaufils, C.; Bizien, L.; Bisiaux, A.; Lei, W.; Hasan, M.; Chen, J.; Gaughan, C.; Asthana, A.; Libri, V.; Luna, J. M.; Jaffré, F.; Hoffmann, H. H.; Michailidis, E.; Moreews, M.; Seeleuthner, Y.; Bilguvar, K.; Mane, S.; Flores, C.; Zhang, Y.; Arias, A. A.; 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, R. M.; Belkaya, S.; Lorenzo, L.; Anton, J.; Delafontaine, S.; Toubiana, J.; Bajolle, F.; Fumadó, V.; DeDiego, M. L.; Fidouh, N.; Rozenberg, F.; Pérez-Tur, J.; Chen, S.; Evans, T.; Geissmann, F.; Lebon, P.; Weiss, S. R.; Bonnet, D.; Duval, X.; CoV-Contact Cohort; COVID Human Genetic Effort; Pan-Hammarström, Q.; Planas, A. M.; Meyts, I.; Haerynck, F.; Pujol, A.; Sancho-Shimizu, V.; Dalgard, C. L.; Bustamante, J.; Puel, A.; Boisson-Dupuis, S.; Boisson, B.; Maniatis, T.; Zhang, Q.; Bastard, P.; Notarangelo, L.; Abel, L.; Béziat, V.; Perez de Diego, R.; Rodriguez-Gallego, C.; Su, H. C.; Lifton, R. P.; Jouanguy, E.; Cobat, A.; Alsina, L.; Keles, S.; Haddad, E.; Belot, A.; Quintana-Murci, L.; Rice, C. M.; Silverman, R. H.; Zhang, S. Y.; Casanova, J. L. |
| Article Title: | Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children |
| 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 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. |
| Keywords: | child; genetics; metabolism; cytokine; cytokines; double stranded rna; rna, double-stranded; endoribonucleases; ribonuclease; humans; human; covid-19; sars-cov-2 |
| Journal Title: | Science |
| Volume: | 379 |
| Issue: | 6632 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2023-02-10 |
| Start Page: | eabo3627 |
| Language: | English |
| DOI: | 10.1126/science.abo3627 |
| PUBMED: | 36538032 |
| PROVIDER: | scopus |
| PMCID: | PMC10451000 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2023 -- Source: Scopus |
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