Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartanska 1, 02-637 Warsaw, Poland.
Biologic Therapy Center, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartanska 1, 02-637 Warsaw, Poland.
Int J Mol Sci. 2023 Oct 23;24(20):15495. doi: 10.3390/ijms242015495.
Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD ( < 0.001), SLE and HC ( = 0.008), SSc and MCTD ( 0.001), and SSc and HC ( < 0.001), but neither between MCTD and HC ( = 0.09) nor SSc and SLE ( = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes ( = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.
混合性结缔组织病（MCTD）是一种非常罕见的疾病，属于罕见且临床多因素疾病。MCTD 的发病机制尚不清楚。最被理解的表观遗传改变是 DNA 甲基化，其作用是调节基因表达。在文献中，越来越多的假设认为 DNA 甲基化可能是自身免疫性结缔组织病（ACTDs）如系统性硬化症（SSc）和系统性红斑狼疮（SLE）发展的原因之一。本研究的目的是定义 MCTD 与其他 ACTD 患者全血样本中的整体 DNA 甲基化变化。该研究纳入了 54 例 MCTD 患者、43 例 SSc 患者、45 例 SLE 患者和 43 名健康对照者（HC）。通过 ELISA 测量整体 DNA 甲基化水平。尽管 MCTD 与对照之间的整体 DNA 甲基化没有显著差异，但我们观察到低甲基化可将 MCTD 患者与 SSc 和 SLE 患者区分开来。本分析显示 SLE 与 MCTD 之间的整体甲基化存在统计学显著差异（<0.001），SLE 与 HC 之间的差异也有统计学意义（=0.008），SSc 与 MCTD 之间的差异也有统计学意义（<0.001），而 MCTD 与 HC 之间的差异无统计学意义（=0.09），SSc 与 SLE 之间的差异也无统计学意义（=0.08）。SLE [0.73（0.43，1.22] 和 SSc [0，91（0.59，1.50]组患者的整体甲基化百分比（中位数，IQR）最高，而 MCTD [0.29（0.20，0.54）]患者和健康对照者[0.51（0.24，0.70）]的结果则相近。此外，我们的研究还提供了 SSc 亚型之间整体 DNA 甲基化水平不同的证据（=0.01）。我们的研究表明，与弥漫性 SSc 相比，局限性 SSc 患者的整体甲基化水平显著升高。我们的数据表明，整体 DNA 甲基化水平可能不是区分 MCTD 与其他 ACTD 的良好诊断标志物。我们的研究为更详细地研究与其他 ACTD 患者相比，MCTD 患者整体 DNA 甲基化水平作为区分因素的意义提供了基础。
