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Epigenetic alterations in autoimmune rheumatic diseases

Nature Reviews Rheumatology volume 7, pages 263–271 (2011)Cite this article

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Abstract

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

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Figure 1: Genetic and epigenetic components determine gene function in health and disease.
Figure 2: DNA methylation, histone modification and gene expression changes in autoimmune disease.
Figure 3: Complex interactions between cells of the immune system, their targets and products underlie the pathology of autoimmune rheumatic diseases and might be epigenetically deregulated.

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Acknowledgements

E. Ballestar is supported by PI081346 (FIS) grant from the Spanish Ministry of Science and Innovation (MICINN) and 2009SGR184 grant from AGAUR (Catalan Government).

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  1. Chromatin and Disease Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avda. Gran Via 199–203, 08907 L'Hospitalet de Llobregat, Barcelona, Spain

    Esteban Ballestar

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Ballestar, E. Epigenetic alterations in autoimmune rheumatic diseases. Nat Rev Rheumatol 7, 263–271 (2011). https://doi.org/10.1038/nrrheum.2011.16

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