Key Points
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Epigenetic mechanisms are essential for immune cell differentiation and function, including the correct activation of B cells and T cells and inflammatory processes
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The dysregulation of epigenetic mechanisms in genetically predisposed individuals is associated with inflammatory rheumatic diseases
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Epigenome-wide association studies in genetically complex inflammatory rheumatic diseases have identified substantial correlations between epigenetic mechanisms and disease activity and severity
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Epigenetic dysregulation contributes to the clinical manifestations of monogenic autoinflammatory syndromes and can be used as a biomarker of response to treatment
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The systematic use of epigenomic screening will help to classify and identify novel biomarkers for personalized management of patients with inflammatory rheumatic diseases
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New inhibitors of epigenetic enzymes or upstream enzymes that are linked to the epigenetic control of immune function are likely to be tested in clinical trials for disease management
Abstract
Over the past decade, awareness of the importance of epigenetic alterations in the pathogenesis of rheumatic diseases has grown in parallel with a general recognition of the fundamental role of epigenetics in the regulation of gene expression. Large-scale efforts to generate genome-wide maps of epigenetic modifications in different cell types, as well as in physiological and pathological contexts, illustrate the increasing recognition of the relevance of epigenetics. To date, although several reports have demonstrated the occurrence of epigenetic alterations in a wide range of inflammatory rheumatic conditions, epigenomic information is rarely used in a clinical setting. By contrast, several epigenetic biomarkers and treatments are currently in use for personalized therapies in patients with cancer. This Review highlights advances from the past 5 years in the field of epigenetics and their application to inflammatory rheumatic diseases, delineating the future lines of development for a rational use of epigenetic information in clinical settings and in personalized medicine. These advances include the identification of epipolymorphisms associated with clinical outcomes, DNA methylation as a contributor to disease susceptibility in rheumatic conditions, the discovery of novel epigenetic mechanisms that modulate disease susceptibility and the development of new epigenetic therapies.
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Ballestar, E., Li, T. New insights into the epigenetics of inflammatory rheumatic diseases. Nat Rev Rheumatol 13, 593–605 (2017). https://doi.org/10.1038/nrrheum.2017.147
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