Epigenetic alterations in autoimmune rheumatic diseases

• Published in: Nature reviews. Rheumatology Vol. 7; no. 5; pp. 263 - 271
• Main Author: Ballestar, Esteban
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2011; Nature Publishing Group
• Subjects: 631/208/176/1988; 692/420/2489/144; 692/699/1670/1613; 692/699/1670/498; Arthritis, Rheumatoid - etiology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Autoimmune diseases; Autoimmune Diseases - etiology; Autoimmune Diseases - genetics; Autoimmune Diseases - metabolism; Care and treatment; Development and progression; DNA Methylation; Enzymes; Epigenetic inheritance; Epigenetics; Epigenomics; Gene expression; Gene Expression Regulation; Genetic aspects; Humans; Lupus; Lupus Erythematosus, Systemic - etiology; Lupus Erythematosus, Systemic - genetics; Major histocompatibility complex; Medicine; Medicine & Public Health; Pathogenesis; Physiological aspects; Proteins; review-article; Rheumatic diseases; Rheumatic Diseases - etiology; Rheumatic Diseases - genetics; Rheumatic Diseases - metabolism; Rheumatoid arthritis; Rheumatology; Roles; Spain
• ISSN: 1759-4790; 1759-4804; 1759-4804
• DOI: 10.1038/nrrheum.2011.16

The potential of epigenetics to explain the complex links between environmental triggers and genetic susceptibility is captivating researchers in many diseases. As this article describes, considerable evidence suggests that aberrant epigenetic modifications contribute to pathogenesis of these diseases, and drugs that can reverse such changes are a tantalizing prospect for future therapy. The potential roles of epigenetic alterations in the pathogenesis of autoimmune rheumatic diseases are raising great expectations among clinicians and researchers. Epigenetic mechanisms regulate gene expression and are sensitive to external stimuli, bridging the gap between environmental and genetic factors. Considerable evidence of epigenetic changes, particularly altered patterns of DNA methylation, exists in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. The importance of such changes in the pathology of rheumatic diseases has been demonstrated by examining the relationship between gene-specific methylation and SLE in monozygotic twins discordant for the disease, in whom genetic variability is excluded as a cause for discordance. Several studies have highlighted the importance of the tissue-specificity of DNA methylation changes, an aspect which—in contrast with genetic analysis—must be considered when designing epigenetic studies. Here I discuss the proposed mechanisms and implications of DNA methylation changes in the pathogenesis of autoimmune rheumatic diseases, the prospects for future epigenetic studies in rheumatology, the relevance of specific DNA methylation markers and the potential use of drugs with an epigenetic effect in the clinical management of these diseases. Key Points Autoimmune rheumatic disorders are complex diseases that involve genetic and environmental components—these facets are linked by epigenetic modifications, which control gene expression and are subject to environmental influences Monozygotic twins discordant for autoimmune disease provide an opportunity to specifically study epigenetic changes that lead to the development of autoimmunity, because genetic variability is excluded Candidate gene approaches have identified a small set of genes that undergo aberrant DNA demethylation and overexpression in systemic lupus erythematosus and rheumatoid arthritis High-throughput approaches are necessary for screening epigenetic alterations in autoimmune disease, and it is essential to screen the specific tissue and cell types that are relevant to disease pathogenesis Identification of cell-specific targets of epigenetic deregulation in autoimmune rheumatic disorders will provide clinical markers for diagnosis, disease progression and response to therapies