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

Annals of the Rheumatic Diseases
Javier Rodríguez-UbrevaEsteban Ballestar

Abstract

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. 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. 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...Continue Reading

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Citations

Jun 27, 2020·Journal of the American Society of Nephrology : JASN·Komal SodhiJoseph I Shapiro
Aug 8, 2020·Nature Reviews. Rheumatology·Esteban BallestarQianjin Lu
Jan 23, 2020·Genes·Carlos de la Calle-FabregatEsteban Ballestar
Feb 28, 2021·Genes & Genomics·Sabrina Ka Man Tam, Danny Chi Yeu Leung
Feb 26, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Pan ShenShenghao Tu
Jan 9, 2021·Bioinformatics·Octavio Morante-Palacios, Esteban Ballestar
Apr 1, 2021·Rheumatology·Yannick DegboéCarl S Goodyear
Oct 10, 2021·Annals of the Rheumatic Diseases·Alejandro Ibáñez-CostaChary Lopez-Pedrera
Jun 10, 2021·Arthritis & Rheumatology·Carlos de la Calle-FabregatEsteban Ballestar

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