ArticleEBioMedicine2022
Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis.
Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Responsiveness of epigenetic aging biomarkers to longevity interventions in humans.Nature medicine · 2026Article
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- CpG Atlas: A centralized multi-layer database and AI interface for DNA methylation research.bioRxiv : the preprint server for biology · 2026Article
- Rheumatoid Arthritis: Biomarkers and the Latest Breakthroughs.International journal of molecular sciences · 2025Review
- DNA Methylation Smoking Scores and Risk of Islet Autoimmunity and Type 1 Diabetes.Diabetes care · 2025Article
- A Novel Multiplex Diagnostic Algorithm for Developing an Optimal Patient-Tailored Therapy in Rheumatoid Arthritis Based on Molecular Stratification.International journal of molecular sciences · 2025Article
- Whole Blood DNA Methylation Changes Are Associated with Anti-TNF Drug Concentration in Patients with Crohn's Disease.Journal of Crohn's & colitis · 2024Article
- PTEN: an emerging target in rheumatoid arthritis?Cell communication and signaling : CCS · 2024Review
- Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease.International journal of molecular sciences · 2024Review
- A novel approach toward optimal workflow selection for DNA methylation biomarker discovery.BMC bioinformatics · 2024Article
- DNA Methylation Signatures of Response to Conventional Synthetic and Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis.Biomedicines · 2023Review
- An overview of DNA methylation-derived trait score methods and applications.Genome biology · 2023Review
- Novel DNA methylome biomarkers associated with adalimumab response in rheumatoid arthritis patients.Frontiers in immunology · 2023Article
- A machine learning approach utilizing DNA methylation as an accurate classifier of COVID-19 disease severity.Scientific reports · 2022Article
- -Omic Approaches and Treatment Response in Rheumatoid Arthritis.Pharmaceutics · 2022Review
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Authors and funding
22 authors.
Funding
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Abstract
backgroundRheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy.
methodsPeripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients.
findingsTreatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi.
interpretationOur results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.
fundingThe Instituto de Salud Carlos III.
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