Repositori URV

Autor segons l'article: Matuozzo, D; Talouarn, E; Marchal, A; Zhang, P; Manry, J; Seeleuthner, Y; Zhang, Y; Bolze, A; Chaldebas, M; Milisavljevic, B; Gervais, A; Bastard, P; Asano, T; Bizien, L; Barzaghi, F; Abolhassani, H; Abou Tayoun, A; Aiuti, A; Alavi Darazam, I; Allende, LM; Alonso-Arias, R; Arias, AA; Aytekin, G; Bergman, P; Bondesan, S; Bryceson, YT; Bustos, IG; Cabrera-Marante, O; Carcel, S; Carrera, P; Casari, G; Chaïbi, K; Colobran, R; Condino-Neto, A; Covill, LE; Delmonte, OM; El Zein, L; Flores, C; Gregersen, PK; Gut, M; Haerynck, F; Halwani, R; Hancerli, S; Hammarström, L; Hatipoglu, N; Karbuz, A; Keles, S; Kyheng, C; Leon-Lopez, R; Franco, JL; Mansouri, D; Martinez-Picado, J; Metin Akcan, O; Migeotte, I; Morange, PE; Morelle, G; Martin-Nalda, A; Novelli, G; Novelli, A; Ozcelik, T; Palabiyik, F; Pan-Hammarström, Q; de Diego, RP; Planas-Serra, L; Pleguezuelo, DE; Prando, C; Pujol, A; Reyes, LF; Rivière, JG; Rodriguez-Gallego, C; Rojas, J; Rovere-Querini, P; Schlüter, A; Shahrooei, M; Sobh, A; Soler-Palacin, P; Tandjaoui-Lambiotte, Y; Tipu, I; Tresoldi, C; Troya, J; van de Beek, D; Zatz, M; Zawadzki, P; Al-Muhsen, SZ; Alosaimi, MF; Alsohime, FM; Baris-Feldman, H; Butte, MJ; Constantinescu, SN; Cooper, MA; Dalgard, CL; Fellay, J; Heath, JR; Lau, YL; Lifton, RP; Maniatis, T; Mogensen, TH; von Bernuth, H; Lermine, A; Vidaud, M; Boland, A; Deleuze, JF; Nussbaum, R; Kahn-Kirby, A; Mentre, F; Tubiana, S; Gorochov, G; Tubach, F; Hausfater, P; Effort, CHG; Meyts, I; Zhang, SY; Puel, A; Notarangelo, LD; Boisson-Dupuis, S; Su, HC; Boisson, B; Jouanguy, E; Casanova, JL; Zhang, Q; Abel, L; Cobat, A

Departament: Medicina i Cirurgia

Autor/s de la URV: Auguet Quintillà, Maria Teresa

Paraules clau: covid-19 disease immunity npc2 type i interferon Covid-19 Immunity Rare variants Type i interferon Wide association

Resum: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in?~?80% of cases.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was <jats:italic>TLR7</jats:italic>, with an OR of 27.68 (95%CI 1.5–528.7, <jats:italic>P</jats:italic>?=?1.1?×?10<jats:sup>?4</jats:sup>) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR?=?3.70[95%CI 1.3–8.2], <jats:italic>P</jats:italic>?=?2.1?×?10<jats:sup>?4</jats:sup>). This enrichment was further strengthened by (1) adding the recently reported <jats:italic>TYK2</jats:italic> and <jats:italic>TLR7</jats:italic> COVID-19 loci, particularly under a recessive model (OR?=?19.65[95%CI 2.1–2635.4], <jats:italic>P</jats:italic>?=?3.4?×?10<jats:sup>?3</jats:sup>), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR?=?4.40[9%CI 2.3–8.4], <jats:italic>P</jats:italic>?=?7.7?×?10<jats:sup>?8</jats:sup>). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]?=?43.3 [20.3] years) than the other patients (56.0 [17.3] years; <jats:italic>P</jats:italic>?=?1.68?×?10<jats:sup>?5</jats:sup>).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.</jats:p> </jats:sec>

Àrees temàtiques: Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Genetics Genetics & heredity Genetics (clinical) Medicina i Medicina ii Molecular biology Molecular medicine Saúde coletiva

Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/

Adreça de correu electrònic de l'autor: mariateresa.auguet@urv.cat

Identificador de l'autor: 0000-0003-0396-6428

Data d'alta del registre: 2023-12-02

Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion

Enllaç font original: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-023-01173-8

Referència a l'article segons font original: Genome Medicine. 15 (1): 22-

Referència de l'ítem segons les normes APA: Matuozzo, D; Talouarn, E; Marchal, A; Zhang, P; Manry, J; Seeleuthner, Y; Zhang, Y; Bolze, A; Chaldebas, M; Milisavljevic, B; Gervais, A; Bastard, P; (2023). Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19. Genome Medicine, 15(1), 22-. DOI: 10.1186/s13073-023-01173-8

URL Document de llicència: http://repositori.urv.cat/ca/proteccio-de-dades/

DOI de l'article: 10.1186/s13073-023-01173-8

Entitat: Universitat Rovira i Virgili

Any de publicació de la revista: 2023

Tipus de publicació: Journal Publications