REVIEW Critical role of DNA methylation in the pathogenesis of systemic lupus erythematosus: new advances and future challenges

Systemic lupus erythematosus (SLE) is a systemic multi-organ autoimmune disease with dif-ferent immunological characteristics and clinical manifestations characterized by an autoanti-body response to nuclear and cytoplasmic antigens; the etiology of this disease remains largely unknown. Most recent genome-wide association studies demonstrate that genetics signifi-cantly predispose to SLE onset, but the incomplete disease concordance rates between mono-zygotic twins indicates a role for other complementary factors in SLE pathogenesis. Recently, much evidence strongly supports other molecular mechanisms involved in the regulation of gene expression ultimately causing autoimmune disease, and several studies, both in clinical settings and experimental models, have demonstrated that epigenetic modifications may hold the key to a better understanding of SLE initiation and development. DNA methylation changes the structure of chromatin, being typically able to modulate the fine interactions between promoter-transcription factors and encoding genes within the transcription machin-ery. Alteration in DNA methylation has been confirmed as a major epigenetic mechanism that may potentially cause a breakdown of immune tolerance and perpetuation of SLE. Based on recent findings, DNA methylation treatments already being used in oncology may soon prove beneficial to patients with SLE. We herein discuss what we currently know, and what we expect in the future. Lupus (2014) 0, 1–13. Key words: Systemic lupus erythematosus; DNA methylation; DNA methyltransferase; microRNA; autoimmune diseas