English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/213599
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis

AuthorsRodríguez-Ubreva, J.; De La Calle-Fabregat, C.; Li, T.; Ciudad, L.; Ballestar, M.L.; Català-Moll, F.; Morante-Palacios, O.; Garcia-Gomez, A.; Celis, R. ; Humby, F.; Nerviani, A.; Martín, J.; Pitzalis, C.; Cañete, J.D.; Ballestar, E.
KeywordsDAS28
DNA methylation
TNFa
disease activity
rheumatoid arthritis
Issue Date2019
PublisherBMJ Publishing Group
CitationAnnals of the Rheumatic Diseases (2019)
AbstractObjective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. Methods: High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinical parameters, including RA disease activity. Results: The DNA methylomes of peripheral blood monocytes displayed significant changes and increased variability in patients with RA with respect to healthy controls. Changes in the monocyte methylome correlate with DAS28, in which high-activity patients are divergent from healthy controls in contrast to remission patients whose methylome is virtually identical to healthy controls. Indeed, the notion of a changing monocyte methylome is supported after comparing the profiles of same individuals at different stages of activity. We show how these changes are mediated by an increase in disease activity-associated cytokines, such as tumour necrosis factor alpha and interferons, as they recapitulate the DNA methylation changes observed in patients in vitro. Conclusion: We demonstrate a direct link between RA disease activity and the monocyte methylome through the action of inflammation-associated cytokines. Finally, we have obtained a DNA methylation-based mathematical formula that predicts inflammation-mediated disease activity for RA and other chronic immune-mediated inflammatory diseases.
Publisher version (URL)http://dx.doi.org/10.1136/annrheumdis-2019-215355
URIhttp://hdl.handle.net/10261/213599
Identifiersdoi: 10.1136/annrheumdis-2019-215355
issn: 1468-2060
Appears in Collections:(IPBLN) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.