{"id":33519,"date":"2025-05-27T12:00:00","date_gmt":"2025-05-27T10:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/27\/from-rare-to-common-genetic-insights-into-tlr7-variants-in-a-multicentric-spanish-study-on-covid-19-severity\/"},"modified":"2025-05-27T12:00:00","modified_gmt":"2025-05-27T10:00:00","slug":"from-rare-to-common-genetic-insights-into-tlr7-variants-in-a-multicentric-spanish-study-on-covid-19-severity","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/27\/from-rare-to-common-genetic-insights-into-tlr7-variants-in-a-multicentric-spanish-study-on-covid-19-severity\/","title":{"rendered":"From Rare to Common: Genetic Insights into TLR7 Variants in a Multicentric Spanish Study on COVID-19 Severity"},"content":{"rendered":"<div>\n<p><b>J Clin Immunol<\/b>. 2025 May 27;45(1):100. doi: 10.1007\/s10875-025-01892-0.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>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&gt;G (rs179009) and c.*881C&gt;G (rs3853839) were associated with severe pneumonia, while c.4-151A&gt;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.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40423910\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_campaign=journals&amp;utm_content=8102137&amp;ff=20250527124924&amp;v=2.18.0.post9+e462414\">40423910<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1007\/s10875-025-01892-0\">10.1007\/s10875-025-01892-0<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Clin Immunol. 2025 May 27;45(1):100. doi: 10.1007\/s10875-025-01892-0. 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 &#8230; <a title=\"From Rare to Common: Genetic Insights into TLR7 Variants in a Multicentric Spanish Study on COVID-19 Severity\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/27\/from-rare-to-common-genetic-insights-into-tlr7-variants-in-a-multicentric-spanish-study-on-covid-19-severity\/\" aria-label=\"Read more about From Rare to Common: Genetic Insights into TLR7 Variants in a Multicentric Spanish Study on COVID-19 Severity\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-33519","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33519","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=33519"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33519\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=33519"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=33519"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=33519"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}