Emerging role of epigenetics in systemic sclerosis pathogenesis.

Systemic sclerosis is a connective tissue disease of unknown aetiology characterised by autoimmunity, inflammation, vascular abnormalities and ultimately fibrosis. Although great advances have been made in determining the molecular mechanisms of disease pathogenesis over the last decade, aided by new genetic screens, no current specific disease-modifying treatment is yet available. Epigenetics is defined as heritable changes that are not due to changes in DNA sequence, and there is at present intense research effort to understand the basic mechanisms of epigenetic regulation and how these impact diseases. Epigenetic modifications and dysregulation are associated now with autoimmune disease, inflammatory disease and cancer. In rheumatic diseases all three epigenetic processes are associated with various diseases including rheumatoid arthritis and systemic sclerosis. In systemic sclerosis much focus has been on microRNAs; however, other modifications including DNA methylation are emerging to have a key role. This review examines the role of epigenetics in systemic sclerosis and appraises the contribution of each modification and suggests that modulators of epigenetic changes may be a novel therapeutic option.