Ehtesham Naeim, Habibi Kavashkohie Mohammad Reza, Mazhari Seyed Amirhossein, Azhdari Sara, Ranjbar Hamta, Mosallaei Meysam, Hazrati Ebrahim, Behroozi Javad
Department of Genetics and Advanced Medical Technology, Faculty of Medicine, 162996AJA University of Medical Sciences, Tehran, Iran.
Student Research Committee, 48533University of Social Welfare and Rehabilitation Science, Tehran, Iran.
Lupus. 2023 Mar;32(3):363-379. doi: 10.1177/09612033221148099. Epub 2022 Dec 27.
Traditionally, the diagnosis and monitoring of disease activity in systemic lupus erythematosus (SLE) are contingent upon clinical manifestations and serological markers. However, researchers are struggling to find biomarkers with higher sensitivity and specificity. DNA methylation has been the most studied epigenetic feature in SLE. So, in this study, we performed a systematic review of studies about DNA methylation alterations in SLE patients compared to healthy controls.
By searching PubMed, Scopus, and Google Scholar up to July 2022, all case-control studies in which DNA methylation of specific genes was assessed by a non-high-throughput technique and passed the quality of bias assessment were included.
In total, 44 eligible studies underwent a data extraction process. In all, 3471 SLE patients and 1028 healthy individuals were included. Among the studies that reported the patients' gender ( = 2853), 89.41% were female and 10.59% were male. Forty studies have been conducted on adult patients. The number of works on fractionated and unfractionated blood cells was almost equal. In this regard, 22 studies were conducted on whole blood or peripheral blood mononuclear cells and two studies on unfractionated white blood cells. Sorted blood cells were biological sources in 20 studies. The most investigated gene was . Sensitivity, specificity, and diagnostic power of methylation levels were only reported for in five studies. The most employed methylation profiling method was bisulfite sequencing polymerase chain reaction. The correlation between methylation patterns and clinical parameters was explored in 22 studies, which of them 16 publications displayed a remarkable association between DNA methylation status and clinical indices.
The methylation status of some genes especially , , and has been suggested as promising SLE biomarkers. However, given the conflicting findings between studies because of potential confounders such as different sample types, methylation profiling methods, and ethnicity as well as shared DNA methylation patterns of SLE and other autoimmune diseases, DNA methylation biomarkers are currently not reliable diagnostic biomarkers and do not represent surrogate markers of SLE disease activity. Future investigations on a larger scale with the discarding of limitations of previous studies would probably lead to a consensus.
传统上，系统性红斑狼疮（SLE）疾病活动的诊断和监测取决于临床表现和血清学标志物。然而，研究人员一直在努力寻找具有更高敏感性和特异性的生物标志物。DNA甲基化是SLE中研究最多的表观遗传特征。因此，在本研究中，我们对与健康对照相比SLE患者DNA甲基化改变的研究进行了系统综述。
通过检索截至2022年7月的PubMed、Scopus和谷歌学术，纳入所有采用非高通量技术评估特定基因DNA甲基化并通过偏倚评估质量的病例对照研究。
总共44项符合条件的研究进行了数据提取。总共纳入了3471例SLE患者和1028名健康个体。在报告患者性别的研究中（n = 2853），89.41%为女性，10.59%为男性。40项研究针对成年患者进行。对分离和未分离血细胞的研究数量几乎相等。在这方面，22项研究针对全血或外周血单个核细胞进行，两项研究针对未分离的白细胞进行。20项研究中分类血细胞是生物来源。研究最多的基因是。仅在5项研究中报告了甲基化水平的敏感性、特异性和诊断能力。最常用的甲基化分析方法是亚硫酸氢盐测序聚合酶链反应。22项研究探讨了甲基化模式与临床参数之间的相关性，其中16篇出版物显示DNA甲基化状态与临床指标之间存在显著关联。
一些基因尤其是、和的甲基化状态已被认为是有前景的SLE生物标志物。然而，由于潜在的混杂因素，如不同的样本类型、甲基化分析方法和种族，以及SLE与其他自身免疫性疾病共有的DNA甲基化模式，各研究结果相互矛盾，目前DNA甲基化生物标志物不是可靠的诊断生物标志物，也不代表SLE疾病活动的替代标志物。未来更大规模的研究，摒弃以往研究的局限性，可能会达成共识。
