DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study
Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD) significantly reduces life quality and survival, necessitating improvements in its understanding and clinical management. We addressed these goals using DNA methylation analysis, which has not been done in RA-ILD samples, by comparin...
| Autores: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/37457 |
| Acceso en línea: | https://hdl.handle.net/10902/37457 |
| Access Level: | acceso abierto |
| Palabra clave: | Rheumatoid arthritis Interstitial lung disease Biomarkers Lung fibrosis DNA methylation Epigenetics |
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DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control studyKaczmarczyk, BartoszDe la Calle Fabregat, CarlosConde, AdrianDuarte, Ana CatarinaMena Vazquez, NataliaFernandez Nebro, AntonioTriguero Martinez, AnaCastañeda, SantosDos Santos Sobrin, RaquelMera Varela, AntonioLopez Pedrera, CharyEscudero Contreras, AlejandroVela Casasempere, PalomaMolina, MariaNarvaez, JavierRetuerto Guerrero, MiriamPablos, Jose L.Sarmiento Monroy, Juan C.Sanmarti, RaimonGonzález-Gay Mantecón, Miguel ÁngelRheumatoid arthritisInterstitial lung diseaseBiomarkersLung fibrosisDNA methylationEpigeneticsRheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD) significantly reduces life quality and survival, necessitating improvements in its understanding and clinical management. We addressed these goals using DNA methylation analysis, which has not been done in RA-ILD samples, by comparing 32 RA patients with ILD diagnosed less than one year before (cases) and 32 matched RA patients without ILD (controls). This analysis identified 6679 differentially methylated positions (DMPs) with ?? ? 2% and FDR < 0.05, and 576 differentially methylated regions in RA-ILD. Some DMPs were near mucin, collagen, and telomere maintenance genes. Also, the most notably enriched gene set (up to padj = 1.9 × 10?38) included genes overexpressed in fibrosis by monocytes and alveolar macrophages. Other significantly enriched gene sets, known to be dysregulated in fibrosis, included the mitotic spindle and the Rho GTPases. Additionally, analysis of transcription factor binding sites around DMPs showed unique enrichment near the liver X receptor element (LXRE), which is associated with fibrosis in multiple tissues. These results were consistent and unaffected by stricter significance thresholds. They indicated that differential DNA methylation may serve as blood biomarkers for RA-ILD including some related to lung fibrosis pathways.Funding for this study was provided by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI23/00841, PI20/01268 and RD21/0002/0003, co-funded by the European Union by the ERDF “A way fo making Europe” and Next Generation EU/PRTR, respectively.Universidad de Cantabria20252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/37457Scientific Reports, 2025, 15, 15123reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/374572026-06-02T12:39:31Z |
| dc.title.none.fl_str_mv |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| title |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| spellingShingle |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study Kaczmarczyk, Bartosz Rheumatoid arthritis Interstitial lung disease Biomarkers Lung fibrosis DNA methylation Epigenetics |
| title_short |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| title_full |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| title_fullStr |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| title_full_unstemmed |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| title_sort |
DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study |
| dc.creator.none.fl_str_mv |
Kaczmarczyk, Bartosz De la Calle Fabregat, Carlos Conde, Adrian Duarte, Ana Catarina Mena Vazquez, Natalia Fernandez Nebro, Antonio Triguero Martinez, Ana Castañeda, Santos Dos Santos Sobrin, Raquel Mera Varela, Antonio Lopez Pedrera, Chary Escudero Contreras, Alejandro Vela Casasempere, Paloma Molina, Maria Narvaez, Javier Retuerto Guerrero, Miriam Pablos, Jose L. Sarmiento Monroy, Juan C. Sanmarti, Raimon González-Gay Mantecón, Miguel Ángel |
| author |
Kaczmarczyk, Bartosz |
| author_facet |
Kaczmarczyk, Bartosz De la Calle Fabregat, Carlos Conde, Adrian Duarte, Ana Catarina Mena Vazquez, Natalia Fernandez Nebro, Antonio Triguero Martinez, Ana Castañeda, Santos Dos Santos Sobrin, Raquel Mera Varela, Antonio Lopez Pedrera, Chary Escudero Contreras, Alejandro Vela Casasempere, Paloma Molina, Maria Narvaez, Javier Retuerto Guerrero, Miriam Pablos, Jose L. Sarmiento Monroy, Juan C. Sanmarti, Raimon González-Gay Mantecón, Miguel Ángel |
| author_role |
author |
| author2 |
De la Calle Fabregat, Carlos Conde, Adrian Duarte, Ana Catarina Mena Vazquez, Natalia Fernandez Nebro, Antonio Triguero Martinez, Ana Castañeda, Santos Dos Santos Sobrin, Raquel Mera Varela, Antonio Lopez Pedrera, Chary Escudero Contreras, Alejandro Vela Casasempere, Paloma Molina, Maria Narvaez, Javier Retuerto Guerrero, Miriam Pablos, Jose L. Sarmiento Monroy, Juan C. Sanmarti, Raimon González-Gay Mantecón, Miguel Ángel |
| author2_role |
author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad de Cantabria |
| dc.subject.none.fl_str_mv |
Rheumatoid arthritis Interstitial lung disease Biomarkers Lung fibrosis DNA methylation Epigenetics |
| topic |
Rheumatoid arthritis Interstitial lung disease Biomarkers Lung fibrosis DNA methylation Epigenetics |
| description |
Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD) significantly reduces life quality and survival, necessitating improvements in its understanding and clinical management. We addressed these goals using DNA methylation analysis, which has not been done in RA-ILD samples, by comparing 32 RA patients with ILD diagnosed less than one year before (cases) and 32 matched RA patients without ILD (controls). This analysis identified 6679 differentially methylated positions (DMPs) with ?? ? 2% and FDR < 0.05, and 576 differentially methylated regions in RA-ILD. Some DMPs were near mucin, collagen, and telomere maintenance genes. Also, the most notably enriched gene set (up to padj = 1.9 × 10?38) included genes overexpressed in fibrosis by monocytes and alveolar macrophages. Other significantly enriched gene sets, known to be dysregulated in fibrosis, included the mitotic spindle and the Rho GTPases. Additionally, analysis of transcription factor binding sites around DMPs showed unique enrichment near the liver X receptor element (LXRE), which is associated with fibrosis in multiple tissues. These results were consistent and unaffected by stricter significance thresholds. They indicated that differential DNA methylation may serve as blood biomarkers for RA-ILD including some related to lung fibrosis pathways. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10902/37457 |
| url |
https://hdl.handle.net/10902/37457 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
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Scientific Reports, 2025, 15, 15123 reponame:UCrea Repositorio Abierto de la Universidad de Cantabria instname:Universidad de Cantabria (UC) |
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Universidad de Cantabria (UC) |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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1869411784857747456 |
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15,81155 |