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https://hdl.handle.net/2445/222239
Title: | From Rare to Common: Genetic Insights into TLR7 Variants in a Multicentric Spanish Study on COVID-19 Severity |
Author: | Antolí, Arnau Vargas Parra, Gardenía María Sierra Fortuny, Àngels Gómez Vázquez, José Luis Rofes, Paula Munté, Elisabet Viana Errasti, Julen Marín Montes, Raúl López Dóriga Guerra, Adriana Feliubadaló, Lidia Valle, Jesús del Pérez González, Alexandre Poveda, Eva Solanich, Xavier Lázaro García, Conxi |
Keywords: | SARS-CoV-2 Epidemiologia genètica SARS-CoV-2 Genetic epidemiology |
Issue Date: | 27-May-2025 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | TLR7, which encodes a key receptor for single-stranded RNA (ssRNA) virus of the innate immune system, was recently associated with X-linked immunodeficiency and COVID-19 susceptibility. This study investigates the association between TLR7 variants and susceptibility to severe COVID-19 in a multicentric Spanish cohort. The TLR7 gene was sequenced in a cohort of 365 COVID-19 patients, stratified into two groups: one comprising mild and asymptomatic patients, considered as controls (n = 87), and the other consisting of moderate to severely affected patients hospitalized due to COVID-19 pneumonia, considered as cases (n = 278). A total of 152 unique TLR7 variants were identified, of note, six rare variants were identified in 11 cases (3.96%), all of whom belonged to the case group. The functional impact of rare TLR7 variants was assessed using a luciferase reporter assay and revealed that N215S is a loss-of-function (LOF) variant, while D332G exhibits an hypomorphic behavior. Conversely, H90Y, V219I, A448V, and R902K maintained normal signaling. No skewed X-inactivation was observed in female carriers of N215S or D332G. In addition, the common variants Q11L (rs179008), c.4-151A>G (rs179009) and c.*881C>G (rs3853839) were associated with severe pneumonia, while c.4-151A>G (rs179009) was specifically linked to Intensive Care Unit (ICU) admission. These findings highlight the role of TLR7 in antiviral immune response and its association with severe COVID-19 in men. The luciferase assay proves to be a reliable tool for evaluating TLR7 signaling, effectively distinguishing between neutral, LOF, and gain-of-function (GOF) variants. Further research is needed to better understand TLR7 variants and its implications in immunodeficiency and immune dysregulation. |
Note: | Reproducció del document publicat a: https://doi.org/10.1007/s10875-025-01892-0 |
It is part of: | Journal of Clinical Immunology, 2025, vol. 45, num. 1, 100 |
URI: | https://hdl.handle.net/2445/222239 |
Related resource: | https://doi.org/10.1007/s10875-025-01892-0 |
ISSN: | 1573-2592 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Ciències Clíniques) |
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