Épigénétique et auto-immunité

Evidences are accumulating to consider that epigenetic mechanisms, and its main process DNA methylation, play a key role in promoting autoimmunity in genetically predestined patients. Indeed, inhibition of DNA methyl transferases (DNMTs) that are responsible for providing DNA methylation is associated by the development of systemic lupus erythematosus (SLE) associated with Sjögren's syndrome (SS). In addition, defects in DNA methylation are specific to a given cell type and related to an autoimmune disease. Indeed, lymphocytes are demethylated in SLE, epithelial cells in SGS, synoviocytes in rheumatoid arthritis (RA), and the white substance in multiple sclerosis (MS). Obstruction of the ERK/DNMT1 pathway is the main mechanism leading to DNA demethylation and this abnormality can be amplified by other mechanisms such as micro-RNAs, drugs or sun lights. Finally, epigenetic mechanisms are reversible. Two examples can be mentioned: in vitro monoclonal antibody (mAb) anti-IL6 receptor (tocilizumab) restores DNA methylation in SLE B cells, and in vivo anti-CD20 mAb (rituximab) allows re-methylation of epithelial cells by killing B cells of the salivary glands of patients with SS. These findings therefore provide new diagnostic, prevention and treatment opportunities in autoimmune diseases.