Inborn Error of STAT2-Dependent IFN-I Immunity in a Patient Presented with Hemophagocytic Lymphohistiocytosis and Multisystem Inflammatory Syndrome in Children

López-Nevado, MartaSevilla, JuliánAlmendro-Vázquez, PatriciaGil-Etayo, Francisco J.Garcinuño, SaraSerrano-Hernández, AntonioPaz Artal, Estela NatividadGonzález Granado, Luis IgnacioAllende Martínez, Luis Miguel2025-01-142025-01-142023-04-19López-Nevado M, Sevilla J, Almendro-Vázquez P, Gil-Etayo FJ, Garcinuño S, Serrano-Hernández A, Paz-Artal E, González-Granado LI, Allende LM. Inborn Error of STAT2-Dependent IFN-I Immunity in a Patient Presented with Hemophagocytic Lymphohistiocytosis and Multisystem Inflammatory Syndrome in Children. J Clin Immunol. 2023 Aug;43(6):1278-1288. doi: 10.1007/s10875-023-01488-6. Epub 2023 Apr 19. PMID: 37074537; PMCID: PMC10113994.0271-91421573-259210.1007/s10875-023-01488-6https://hdl.handle.net/20.500.14352/114117Human inborn errors of immunity (IEI) affecting the type I interferon (IFN-I) induction pathway have been associated with predisposition to severe viral infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome that has been increasingly associated with inborn errors of IFN-I-mediated innate immunity. Here is reported a novel case of complete deficiency of STAT2 in a 3-year-old child that presented with typical features of HLH after mumps, measles, and rubella vaccination at the age of 12 months. Due to the life-threatening risk of viral infection, she received SARS-CoV-2 mRNA vaccination. Unfortunately, she developed multisystem inflammatory syndrome in children (MIS-C) after SARS-CoV-2 infection, 4 months after the last dose. Functional studies showed an impaired IFN-I-induced response and a defective IFNα expression at later stages of STAT2 pathway induction. These results suggest a possible more complex mechanism for hyperinflammatory reactions in this type of patients involving a possible defect in the IFN-I production. Understanding the cellular and molecular links between IFN-I-induced signaling and hyperinflammatory syndromes can be critical for the diagnosis and tailored management of these patients with predisposition to severe viral infection.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Inborn Error of STAT2-Dependent IFN-I Immunity in a Patient Presented with Hemophagocytic Lymphohistiocytosis and Multisystem Inflammatory Syndrome in Childrenjournal articlehttps://doi.org/10.1007/s10875-023-01488-6open access616.98:578.834AnticuerposCovid 19SARS-CoV-2Factor de transcripción STAT2 / genéticaCiencias Biomédicas32 Ciencias Médicas