Oxidative Stress and Epigenetics: miRNA Involvement in Rare Autoimmune Diseases

Autoimmune diseases (ADs) such as Sjögren's syndrome, Kawasaki disease, and systemic sclerosis are characterized by chronic inflammation, oxidative stress, and autoantibodies, which cause joint tissue damage, vascular injury, fibrosis, and debilitation. Epigenetics participate in immune cell proliferation and differentiation, which regulates the development and function of the immune system, and ultimately interacts with other tissues. Indeed, overlapping of certain clinical features between ADs indicate that numerous immunologic-related mechanisms may directly participate in the onset and progression of these diseases. Despite the increasing number of studies that have attempted to elucidate the relationship between miRNAs and oxidative stress, autoimmune disorders and oxidative stress, and inflammation and miRNAs, an overall picture of the complex regulation of these three actors in the pathogenesis of ADs has yet to be formed. This review aims to shed light from a critical perspective on the key AD-related mechanisms by explaining the intricate regulatory ROS/miRNA/inflammation axis and the phenotypic features of these rare autoimmune diseases. The inflamma-miRs miR-155 and miR-146, and the redox-sensitive miR miR-223 have relevant roles in the inflammatory response and antioxidant system regulation of these diseases. ADs are characterized by clinical heterogeneity, which impedes early diagnosis and effective personalized treatment. Redox-sensitive miRNAs and inflamma-miRs can help improve personalized medicine in these complex and heterogeneous diseases.