Chapter 10 - Systemic Sclerosis and Epigenetics

Abstract

Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterized by inflammatory-mediated fibrosis. The disease is heterogeneous and has a variable clinical course. Although some genetic associations have been identified, it is becoming increasingly evident that epigenetic modifications also play an important role. These epigenetic modifications include noncoding RNAs (both long and short forms), DNA methylation, and histone modifications, and all three have been found to be perturbed in SSc. RNA sequencing has helped to examine the role of noncoding RNAs, particularly microRNAs, and identifying the targets of these RNA molecules is now underway. Histone modifications in various cells involved in disease pathogenesis, and changes to the enzymes that regulate these histones, have also been shown to be dysregulated in the disease. It is likely that one modification affects another and works in feed-forward loops. This chapter will appraise the literature regarding the epigenetics of SSc and try and evaluate its therapeutic targeting.