ArticleQJM : monthly journal of the Association of Physicians2018
Toll-like receptor 3 L412F polymorphism promotes a persistent clinical phenotype in pulmonary sarcoidosis.
Article in QJM : monthly journal of the Association of Physicians, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Specific Biomarkers Involved in Sarcoidosis Diagnosis and Prognosis.International journal of molecular sciences · 2026Article
- Toll-like receptor 3 (TLR 3) polymorphisms predisposition to schizophrenia and bipolar disorder.Molecular biology reports · 2025Article
- Fibrotic Pulmonary Sarcoidosis-From Pathogenesis to Management.Journal of clinical medicine · 2025Review
- Phenotypes and Endotypes in Sarcoidosis: Unraveling Prognosis and Disease Course.Biomedicines · 2025Review
- Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis.The Journal of clinical investigation · 2024Review
- Lung fibrosis in sarcoidosis. Is there a place for antifibrotics?Frontiers in pharmacology · 2024Review
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
- Functional link between sarcoidosis-associated gene variants and quantitative levels of bronchoalveolar lavage fluid cell types.Frontiers in medicine · 2023Article
- Immune mechanisms in fibrotic pulmonary sarcoidosis.European respiratory review : an official journal of the European Respiratory Society · 2022Review
- Candidate Role for Toll-like Receptor 3 L412F Polymorphism and Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2022Article
- Exome Sequencing Reveals Genetic Variability and Identifies Chronic Prognostic Loci in Chinese Sarcoidosis Patients.Frontiers in oncology · 2022Article
- Interrelation Between Fibroblasts and T Cells in Fibrosing Interstitial Lung Diseases.Frontiers in immunology · 2021Review
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
introductionSarcoidosis is a multi-systemic disorder of unknown etiology, characterized by the presence of non-caseating granulomas in target organs. In 90% of cases, there is thoracic involvement. Fifty to seventy percent of pulmonary sarcoidosis patients will experience acute, self-limiting disease. For the subgroup of patients who develop persistent disease, no targeted therapy is currently available.
aimTo investigate the potential of the single nucleotide polymorphism (SNP), Toll-like receptor 3 Leu412Phe (TLR3 L412F; rs3775291), as a causative factor in the development of and in disease persistence in pulmonary sarcoidosis. To investigate the functionality of TLR3 L412F in vitro in primary human lung fibroblasts from pulmonary sarcoidosis patients.
designSNP-genotyping and cellular assays, respectively, were used to investigate the role of TLR3 L412F in the development of persistent pulmonary sarcoidosis.
methodsCohorts of Irish sarcoidosis patients (n = 228), healthy Irish controls (n = 263) and a secondary cohort of American sarcoidosis patients (n = 123) were genotyped for TLR3 L412F. Additionally, the effect of TLR3 L412F in primary lung fibroblasts from pulmonary sarcoidosis patients was quantitated following TLR3 activation in the context of cytokine and type I interferon production, TLR3 expression and apoptotic- and fibroproliferative-responses.
resultsWe report a significant association between TLR3 L412F and persistent clinical disease in two cohorts of Irish and American Caucasians with pulmonary sarcoidosis. Furthermore, activation of TLR3 in primary lung fibroblasts from 412 F-homozygous pulmonary sarcoidosis patients resulted in reduced IFN-β and TLR3 expression, reduced apoptosis- and dysregulated fibroproliferative-responses compared with TLR3 wild-type patients. DISCUSSION/
conclusionThis study identifies defective TLR3 function as a previously unidentified factor in persistent clinical disease in pulmonary sarcoidosis and reveals TLR3 L412F as a candidate biomarker.
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