The epigenetics of rheumatic disease

Posted by Biome on 16th May 2013 - 0 Comments


An increasing number of studies have described alterations of epigenetic mechanisms in inflammatory rheumatic diseases, highlighting the importance of epigenetic changes in the development of these diseases.

In November 2012 Arthritis Research & Therapy launched a thematic review series titled ‘Epigenetics and rheumatic diseases’ with the aim of describing the most recent advances in this field. The articles, written by experts from across the globe, discuss the molecular and cellular mechanisms underlining epigenetic-mediated autoimmunity and inflammation as well as the implications for the development of therapies targeted toward epigenetic modulation for these autoimmune disorders. The Series Editor is Nan Shen, Professor of Medicine and Director of Shanghai Institute of Rheumatology, Ren Ji Hospital Shanghai Jiao Tong University, Shanghai, China. Research in Professor Shen’s laboratory focuses on the molecular dissection of disease pathways in systemic autoimmune diseases and the development of novel biomarkers and therapeutic targets in the management of systemic lupus erythematosus (SLE).

The contributions thus far have ranged from a review of the epigenetic alterations in the development of rheumatoid arthritis (by Steffen Gay and colleagues) to a discussion of the role of microRNAs (miRNAs) in the development of systemic autoimmunity (by Ruozhen Hu and Ryan M O’Connell). The most recently published review includes the Series Editor amongst its authors and focuses on the miRNA-mediated regulation of innate immune response in rheumatic diseases. Following an overview of the latest developments in the understanding of miRNA biology, the authors go on to discuss the role of these molecules in regulating the innate immune response and subsequently the dysregulation of this response in rheumatic diseases. Several miRNAs known to be involved in mediating the innate immune response, including miR-146a, miR-155 and miR-23b, have been found to be over- or under-expressed in patients with diseases such as SLE, rheumatoid arthritis (RA), scleroderma etc. Interestingly miR-146a is under-expressed in individuals with SLE, but the levels of this miRNA are elevated in RA, Sjögren’s syndrome and myositis cases. Read the full article for more information on this fascinating topic .

Another recent review by Steven G Gray, a researcher at Trinity College Dublin, explores the use of epigenetic targeting agents as potential new treatment options for rheumatic diseases, especially those with an autoimmune component. Promising results have emerged from studies involving the use of histone deacetylase inhibitors trichostatin A and suberonylanilide hydroxamic acid (vorinostat). Additionally the histone H3K4me3 was recently implicated in SLE pathogenesis, suggesting that an H3K4me3/me2-lysine demethylase and a novel inhibitor, 2,4-pyridine-dicarboxylic acid, could have potential in the treatment of SLE. The author also discussed the use of nutrition based interventions since most rheumatic diseases are chronic conditions that require long-term treatment. A number of naturally occurring compounds, such as curcumin (a natural polyphenol occurring in turmeric), have been shown to inhibit various components of the epigenetic pathways. This review, and others, can be accessed via the thematic series website.