Systemic Lupus Erythematosus and Epigenetics

Abstract

Human systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by autoantibodies to nuclear components with subsequent complex formation and deposition in multiple organs. A combination of genetic and environmental factors is required for disease development. Apoptotic defects and impaired removal of apoptotic cells contribute to an overload of autoantigens that become available to initiate an autoimmune response. Epigenetic factors have significant effects on T-cell functions by modulating its DNA methylation pattern and in patients with active lupus happens gene-specific DNA methylation. Also IL-2 contribute in the pathogenesis by reason of IL-2 regulate the tolerance mechanisms such as the activation induced cell death (AICD) and the induction and maintenance of regulatory T-cells. DNA hypomethylation in CD4+ T-cells causes several gene activations and molecule overexpressions that alters cellular function. Moreover, histone deacetylase inhibitors reverse the skewed expression of multiple genes involved in SLE. 5-azacytidine and other demethylating agents could induce lupuslike autoimmunity in vitro and in vivo. SLE is a predominantly female disease that affects more the female than the male. The etiology of SLE remains incompletely understood, although a number of genetic and environmental factors have been implicated, that may alter epigenetic regulation of gene expression. Epigenetics refers to heritable chromatin-based mechanisms in the regulation of gene expression without changing the DNA sequence. These mechanisms include DNA methylation, histone modification, abnormalities s in ERK pathway signaling, and IL-2 transcriptional irregularity may be the key players through changes on gene expression in the development of this autoimmune disorder