Abstract
Rheumatoid arthritis (RA) is a long-term autoimmune disease of unknown etiology that leads to progressive joint destruction and ultimately to disability. RA affects as much as 1% of the population worldwide. To date, RA is not a curable disease, and the mechanisms responsible for RA development have not yet been well understood. The development of more effective treatments and improvements in the early diagnosis of RA is direly needed to increase patients’ functional capacity and their quality of life. As opposed to genetic mutation, epigenetic changes, such as DNA methylation, are reversible, making them good therapeutic candidates, modulating the immune response or aggressive synovial fibroblasts (FLS—fibroblast-like synoviocytes) activity when it is necessary. It has been suggested that DNA methylation might contribute to RA development, however, with insufficient and conflicting results. Besides, recent studies have shown that circulating cell-free methylated DNA (ccfDNA) in blood offers a very convenient, non-invasive, and repeatable “liquid biopsy”, thus providing a reliable template for assessing molecular markers of various diseases, including RA. Thus, epigenetic therapies controlling autoimmunity and systemic inflammation may find wider implications for the diagnosis and management of RA. In this review, we highlight current challenges associated with the treatment of RA and other autoimmune diseases and discuss how targeting DNA methylation may improve diagnostic, prognostic, and therapeutic approaches.
Highlights
Rheumatic diseases are autoimmune disorders characterized primarily by pain and inflammation.Arthritis, which means “joint inflammation”, belongs to lifestyle diseases
We have shown that specific histones modification induced by histone methyltransferase inhibitor 3-Deazaneplanocin A (DZNep), but not by apicidine can induce strong Tissue inhibitor matrix metalloproteinase-1 (TIMP-1) production in systemic sclerosis (SSc) monocytes and promotes pathogenic properties of myofibroblasts [95]
Much more research can be observed in studies on DNA methylation in the treatment and diagnosis of cancer and proliferative diseases
Summary
Rheumatic diseases are autoimmune disorders characterized primarily by pain and inflammation. The most important therapeutic aims for treating RA are eliminating symptoms (such as joint pain, swelling, and stiffness), preventing further joint damage, maximizing physical function, and improving the quality of life These targets are accomplished by achieving disease remission, a state in which no or only minimal residual inflammation is discernible. Drugs that are currently available are glucocorticoids, nonsteroidal anti-inflammatory drugs or pain medications, synthetic disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate, targeted synthetic DMARDs, which interfere with enzymes, such as Janus kinases (JAKs), biologic DMARDs (Tumor necrosis factor-α (TNF-α) inhibitors, inhibitors of interleukin 6 (IL-6), targets of CD20, inhibitors of CD80/86) These medicines, have various side effects that limit their use.
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