ReviewEpigenetics and lupus
Introduction
Systemic lupus erythematosus (SLE) produces protean clinical manifestations including arthralgia or arthritis, skin lesions, and systemic disorders that determine the severity of the disease and can involve the kidneys, central nervous system, heart, and other organs. The underlying autoimmunity results in the production of autoantibodies such as antinuclear antibodies (ANAs) with antibodies to double-stranded DNA. SLE is a rare disease with a prevalence of only 0.05% among the general population of adults.
The pathophysiological mechanisms that underlie the loss of tolerance to self antigens in SLE are incompletely understood but involve dysfunctions of both adaptive immunity (B cells, T cells, and antigen-presenting cells) and innate immunity (e.g., type I interferon signature) [1], [2], [3], [4].
SLE is among the systemic autoimmune diseases related to complex pathophysiological mechanisms that involve both genetic and environmental factors. Recent technological advances have allowed breakthroughs in the identification of susceptibility factors. Thus, to date, genome-wide association (GWA) screening of several thousand biallelic variants (single nucleotide polymorphisms, SNPs) in case-control studies have identified over 30 genes involved in SLE [5]. A role for epigenetic dysregulation in the pathogenesis of SLE was suggested more recently [6]. This review discusses the mechanisms of epigenetic regulation and describes some of the epigenetic dysregulations identified to date in patients with SLE.
Section snippets
Epigenetic regulation mechanisms
Epigenetics is the study of transmissible and reversible changes in gene expression that are not accompanied with alterations in nucleotide sequences. Epigenetic information is carried chiefly by DNA itself, histones, and noncoding RNAs.
DNA methylation abnormalities
DNA hypomethylation may be among the mechanisms involved in the development of idiopathic SLE and induced SLE. This hypothesis has been investigated by comparing DNA methylation profiles in pairs of twins discordant for SLE. Although monozygotic twins are believed to have identical genetic pools, the concordance rate for SLE is only 24% [9], indicating a major role for environmental factors and epigenetic dysregulation in the pathogenesis of this autoimmune disease. Many genes potentially
Conclusions
The last decade has witnessed an accumulation of information on epigenetic dysregulation as a pathogenic factor in SLE. Research in this field is expanding at a brisk pace. Improved knowledge of epigenetic mechanisms will also shed light on the extraordinary complexity of the modalities of gene regulation and expression. There is good reason to hope that studies into these regulatory mechanisms will considerably broaden the field of new therapeutic developments in the near future.
Disclosure of interest
The author declares that he has no conflicts of interest concerning this article.
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