[Epigenetic disturbances in systemic lupus erythematosus]

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors. They can affect gene expression and are potentially hereditary, but do not lead to changes in the nucleotide sequence. Epigenetic dysfunctions, identified in the course of the disease, lead to changes in the expression of genes that play a key role in maintaining the body's immune tolerance. Major mechanisms of epigenetic variability are: DNA methylation, histone protein modification, non-coding RNA expression, as well as gene imprinting. The major epigenetic dysfunctions affecting the pathogenesis of the disease are global hypomethylation on CD4+ T cells resulting from ERK signaling pathway regulation, histone hypoacetylation, histone H3 lysine methylation, and reactivation of inactive chromosome X. In lupus patients, various epigenetic mechanisms interact with each other, enhancing the expression or silencing of genes responsible for the production of pro-inflammatory and anti-inflammatory cytokines and activation of autoreactive B-lymphocytes.