Department of Pathophysiology and Immunology, National Institute of Geriatrics Rheumatology and Rehabilitation, 02-635 Warsaw, Poland.
Department of Rheumatology, National Institute of Geriatrics Rheumatology and Rehabilitation, 02-635 Warsaw, Poland.
Cells. 2019 Aug 22;8(9):953. doi: 10.3390/cells8090953.
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.
类风湿关节炎（RA）是一种病因不明的长期自身免疫性疾病，可导致进行性关节破坏，最终导致残疾。RA 影响全球多达 1%的人口。迄今为止，RA 无法治愈，其发病机制尚未得到很好的理解。迫切需要开发更有效的治疗方法和改善 RA 的早期诊断，以提高患者的功能能力和生活质量。与基因突变不同，表观遗传变化，如 DNA 甲基化，是可逆的，使其成为良好的治疗候选物，在必要时调节免疫反应或侵袭性滑膜成纤维细胞（FLS-成纤维样滑膜细胞）的活性。已经有人提出，DNA 甲基化可能有助于 RA 的发展，然而，结果却不够充分，也存在冲突。此外，最近的研究表明，血液中的循环无细胞游离甲基化 DNA（ccfDNA）提供了一种非常方便、非侵入性和可重复的“液体活检”，从而为评估包括 RA 在内的各种疾病的分子标志物提供了可靠的模板。因此，控制自身免疫和全身炎症的表观遗传疗法可能会为 RA 的诊断和管理找到更广泛的应用。在这篇综述中，我们强调了与 RA 和其他自身免疫性疾病治疗相关的当前挑战，并讨论了靶向 DNA 甲基化如何改善诊断、预后和治疗方法。
