Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Department of Paediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Curr Rheumatol Rep. 2020 Jul 11;22(8):46. doi: 10.1007/s11926-020-00912-9.
Epigenetics is the study of inherited phenotype changes that do not involve in alteration of DNA sequence. Epigenetic regulation can be examined under three main headings and study methodologies for all three will be discussed: DNA methylation is the addition of a methyl (CH) group to DNA, histone modifications is a covalent post-translational modification of histones and non-coding RNAs are a group of functional RNA molecules that is copied from DNA but not converted into proteins. Epigenetic changes are being increasingly studied in the pathogenesis of most diseases including autoimmune and autoinflammatory diseases to shed light on the different phenotypes and disease courses. We have aimed to review the basic concepts in epigenetic studies and summarize the data for epigenetics in autoimmune and autoinflammatory rheumatic diseases.
Recent studies have assessed DNA hypomethylation in interferon-regulated genes in autoimmune diseases and in inflammatory pathways in systemic autoinflammatory diseases (SAIDs). Abnormal histone acetylation and methylation have been shown to be important in autoimmune diseases which was proven via effective targeted treatment trials against these pathways in mice models. miRNAs have an important role in the pathogenesis, and also, they can be used as diagnostic biomarkers in SAIDs (i.e., FMF, Behcet's disease) together with autoimmune diseases. Although the number of studies has increased over the years in parallel with the increase of interest in this field, we await further studies to improve the understanding and management of pediatric rheumatic diseases. Epigenetic studies in pediatric rheumatic diseases have enabled us to gain new information about disease pathogenesis, clinical heterogeneity, and prognosis. Further studies will help us define new diagnostic, prognostic, and therapeutic goals for rheumatic diseases.
表观遗传学是研究不涉及 DNA 序列改变的遗传表型变化。表观遗传调控可以从三个主要方面进行研究，我们将讨论所有三个方面的研究方法：DNA 甲基化是指在 DNA 上添加一个甲基（CH）基团，组蛋白修饰是组蛋白的共价翻译后修饰，非编码 RNA 是一组从 DNA 复制但不转化为蛋白质的功能性 RNA 分子。表观遗传变化在大多数疾病（包括自身免疫和自身炎症性疾病）的发病机制中越来越受到研究，以阐明不同的表型和疾病过程。我们旨在回顾表观遗传学研究的基本概念，并总结自身免疫和自身炎症性风湿性疾病的表观遗传学数据。
最近的研究评估了自身免疫性疾病中干扰素调节基因的 DNA 低甲基化和系统性自身炎症性疾病（SAIDs）中炎症途径的 DNA 低甲基化。异常的组蛋白乙酰化和甲基化在自身免疫性疾病中很重要，这在小鼠模型中针对这些途径的有效靶向治疗试验中得到了证明。miRNA 在发病机制中具有重要作用，也可以作为 SAIDs（即 FMF、贝赫切特病）和自身免疫性疾病的诊断生物标志物。尽管随着人们对该领域兴趣的增加，这些年来研究数量有所增加，但我们仍在等待进一步的研究来改善对儿科风湿性疾病的理解和管理。儿科风湿性疾病的表观遗传学研究使我们能够获得有关疾病发病机制、临床异质性和预后的新信息。进一步的研究将有助于我们为风湿性疾病定义新的诊断、预后和治疗目标。
