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 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 Δβ ≥ 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 p<sub>adj</sub> = 1.9 × 10<sup>-38</sup>) 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.

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Publication Details

Journal
Scientific Reports
Published
2025-04-29
DOI
https://doi.org/10.1038/s41598-025-99755-6
Citations
3
Primary Topic
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Type
article
Field-Weighted Citation Impact
4.56

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article

DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study

Luis Gómez-Carrera, Javier Narváez, Santos Castañeda, Miguel Ángel González-Gay et al.
3 citations
Scientific Reports
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
4.56
article

DNA methylome biomarkers of rheumatoid arthritis-associated interstitial lung disease reflecting lung fibrosis pathways, an exploratory case–control study

Luis Gómez-Carrera, Javier Narváez, Santos Castañeda, Miguel Ángel González-Gay, Ana Triguero‐Martínez, Ana Cristina Castillo-González, Antonio Fernández‐Nebro, José L. Pablos, Raimón Sanmartí, Carlos de la Calle‐Fabregat, Carlos Marras, Paloma Vela, Eva Pérez‐Pampín, María Molina‐Molina, Juan Camilo Sarmiento-Monroy, L. Mateo-Soria, Sara Remuzgo‐Martínez, Lydia Abásolo, I. Casafont-Solé, C. López-Pedrera, Virginia Leiro‐Fernández, A. Peralta Conde, Antonio Mera, Natalia Mena‐Vázquez, M. Retuerto-Guerrero, Esteban Ballestar, Bartosz Kaczmarczyk, Cristina Vadillo-Font, Antonio González, Ana Catarina Duarte, Gema Bonilla, Alejandro Escudero-Contreras, Naír Pérez-Gómez, R. Dos-Santos Sobrín
article en
3 citations

Abstract

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 Δβ ≥ 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 p<sub>adj</sub> = 1.9 × 10<sup>-38</sup>) 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.

Scientific ReportsVol. 15(1)
Universidad de Cantabria (ES), Universidade de Santiago de Compostela (ES), Hospital Universitario La Paz (ES), Bellvitge University Hospital (ES), University Hospital Complex Of Vigo (ES), Research Institute Hospital 12 de Octubre (ES), Josep Carreras Leukaemia Research Institute (ES), Galicia Sur Biomedical Foundation (ES), Instituto Maimónides de Investigación Biomédica de Córdoba (ES), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES), Marqués de Valdecilla University Hospital (ES), Hospital La Paz Institute for Health Research (ES), Hospital Regional Universitario de Málaga (ES), Hospital Clínic de Barcelona (ES), Hospital Universitario Fundación Jiménez Díaz (ES), Hospital Universitario de La Princesa (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Hospital Garcia de Orta (PT), Instituto de Investigación Sanitaria de Santiago (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitari Germans Trias i Pujol (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación Biomédica de Málaga (ES), Universidad de Málaga (ES)
European Commission, Instituto de Salud Carlos III, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 6%
Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
4.56
DOIOpen Access PDFOpenAlex
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