title: Dissecting complex epigenetic alterations in human lupus.
abstract: Systemic lupus erythematosus is a chronic relapsing autoimmune disease that primarily afflicts women, and both a genetic predisposition and appropriate environmental exposures are required for lupus to develop and flare. The genetic requirement is evidenced by an increased concordance in identical twins and by the validation of at least 35 single-nucleotide polymorphisms predisposing patients to lupus. Genes alone, though, are not enough. The concordance of lupus in identical twins is often incomplete, and when concordant, the age of onset is usually different. Lupus is also not present at birth, but once the disease develops, it typically follows a chronic relapsing course. Thus, genes alone are insufficient to cause human lupus, and additional factors encountered in the environment and over time are required to initiate the disease and subsequent flares. The nature of the environmental contribution, though, and the mechanisms by which environmental agents modify the immune response to cause lupus onset and flares in genetically predisposed people have been controversial. Reports that the lupus-inducing drugs procainamide and hydralazine are epigenetic modifiers, that epigenetically modified T cells are sufficient to cause lupus-like autoimmunity in animal models, and that patients with active lupus have epigenetic changes similar to those caused by procainamide and hydralazine have prompted a growing interest in how epigenetic alterations contribute to this disease. Understanding how epigenetic mechanisms modify T cells to contribute to lupus requires an understanding of how epigenetic mechanisms regulate gene expression. The roles of DNA methylation, histone modifications, and microRNAs in lupus pathogenesis will be reviewed here.
authors: Dipak R
authors: DR
authors: Patel
authors: Bruce C
authors: BC
authors: Richardson
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
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