Epigenetics of autoimmune diseases

Abstract

Although strong genetic bases have been found by genome-wide association studies, no unique genetic mechanism underlying immune tolerance breakdown was identified in autoimmune diseases. The largely incomplete concordance rates of autoimmune diseases in monozygotic twins strongly support other complementary mechanisms involved in gene regulation ultimately causing overt autoimmunity, and it is becoming increasingly evident that epigenetic deregulation contributes to the emergence and/or the progression of disorders that include lupus, rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, vasculitis, diabetes, and multiple sclerosis. A number of epigenetic modifications (DNA methylation, histone acetylation, deacetylation, and methylation, microRNA) have emerged as important contributing factors, and, in some cases, the changes correlate with increased disease activity. The view that epigenetic factors may be of key impact on the pathogenesis of autoimmune diseases is supported by observations that environmental triggers are involved in disease development, since age, infections, smoking, nutrition, and pollution have been suggested to have an effect on the epigenetic background. Importantly, because epigenetic defects, when compared to genetic defects, are more easily reversible with pharmacological intervention, epigenetic therapy promises to offer agents capable of controlling various autoimmune diseases.