Autoimmune disease in the epigenetic era: how has epigenetics changed our understanding of disease and how can we expect the field to evolve?

Autoimmune diseases are complex and enigmatic, and have presented particular challenges to researchers seeking to define their etiology and explain progression. Previous studies have implicated epigenetic influences in the development of autoimmunity. Epigenetics describes changes in gene expression related to environmental influences without alterations in the underlying genomic sequence, generally classified into three main groups: cytosine genomic DNA methylation, modification of various sidechain positions of histone proteins and noncoding RNAs feedback. The purpose of this article is to review the most relevant literature describing alterations of epigenetic marks in the development and progression of four common autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and Sjögren's syndrome. The contribution of DNA methylation, histone modification and noncoding RNA for each of these disorders is discussed, including examples both of candidate gene studies and larger epigenomics surveys, and in various tissue types important for the pathogenesis of each. The future of the field is speculated briefly, as is the possibility of therapeutic interventions targeting the epigenome.