Chapter 1 - The Epigenetics of Autoimmunity: An Overview

Abstract

Autoimmunity refers to the dysregulated immune state that causes loss of immunological tolerance to self-antigens and damage to normal cells and tissues. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors (i.e., nutrition, infection, and chemicals) have been implicated; however, the mechanisms remain unclear. Research advances in the regulation of epigenetic mechanisms (i.e., DNA methylation, histone modification, and noncoding RNA) have shed light on the complexities of autoimmunity. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of systemic lupus erythematosus (SLE), and are known to contribute to its autoimmune pathogenesis. This overview briefly discusses how genetic studies have failed to completely elucidate the pathogenesis of autoimmune diseases, and presents a comprehensive review of the landmark epigenetic findings in autoimmune diseases, using SLE as an extensively studied example. Importantly, emphasis is placed on the fact that the stochastic processes that lead to DNA modifications may be the lynch pins that drive the initial break in tolerance.