Significance: Epigenetic dysregulation plays an important role in the pathogenesis and development of autoimmune diseases. Oxidative stress is associated with autoimmunity and is also known to alter epigenetic mechanisms. Understanding the interplay between oxidative stress and epigenetics will provide insights into the role of environmental triggers in the development of autoimmunity in genetically susceptible individuals. Recent Advances: Abnormal DNA and histone methylation patterns in genes and pathways involved in interferon and tumor necrosis factor signaling, cellular survival, proliferation, metabolism, organ development, and autoantibody production have been described in autoimmunity. Inhibitors of DNA and histone methyltransferases showed potential therapeutic effects in animal models of autoimmune diseases. Oxidative stress can regulate epigenetic mechanisms via effects on DNA damage repair mechanisms, cellular metabolism and the local redox environment, and redox-sensitive transcription factors and pathways. Critical Issues: Studies looking into oxidative stress and epigenetics in autoimmunity are relatively limited. The number of available longitudinal studies to explore the role of DNA methylation in the development of autoimmune diseases is small. Future Directions: Exploring the relationship between oxidative stress and epigenetics in autoimmunity will provide clues for potential preventative measures and treatment strategies. Inception cohorts with longitudinal follow-up would help to evaluate epigenetic marks as potential biomarkers for disease development, progression, and treatment response in autoimmunity. Antioxid. Redox Signal. 36, 423-440.
Keywords: DNA methylation; autoimmunity; biomarker; epigenetics; histone modification; oxidative stress; reactive nitrogen species (RNS); reactive oxygen species (ROS).