ABSTRACT

Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating, and neurodegenerative disorder of the central nervous system. Interactions between environmental factors, predisposition genes, and determining genes appear to be involved in its etiology. Epigenetic mechanisms such as microRNA-mediated gene regulation can determine the susceptibility and severity of autoimmune diseases. Therefore, to determine the role of miR-146a and miR-155 in MS and its developmental stages, the expression levels in the serum of MS and clinically isolated syndrome (CIS) patients were compared with those of healthy controls. In the present study, the expression levels of miR-146a and miR-155 were assessed using quantitative Real-Time PCR in blood samples of 15 CIS patients and 61 relapsing-remitting multiple sclerosis (RRMS) patients alongside 32 healthy patients as controls. Furthermore, any associations with the clinicopathologic variables of the patients were also evaluated. Dysregulations were found only in the miR-146a and miR-155 expressions in the RRMS-Control group. When the RRMS patients were evaluated in terms of the characteristics of sex, annual attack rate, age of diagnosis, duration of follow-up, and immunomodulatory treatments used, no significant differences were observed. However, significant dysregulations were identified in miRNA expression in the vitamin D level, EDSS values, and the number of attacks. ROC curve analysis showed that miR-146a and miR-155 were significant in the RRMS-Control group for the area under the curve (AUC). It is possible that miR-146a may be associated with vitamin D deficiency and disease disability, while miR-155 may be associated with the number of attacks.

摘要

多发性硬化症 (MS) 是一种中枢神经系统的炎症性、自身免疫性脱髓鞘性和神经退行性疾病。环境因素、易感基因和决定基因之间的相互作用似乎与它的病因有关。microRNA 介导的基因调控等表观遗传机制可以决定自身免疫性疾病的易感性和严重程度。因此，为了确定 miR-146a 和 miR-155 在 MS 及其发展阶段中的作用，将 MS 和临床孤立综合征 (CIS) 患者血清中的表达水平与健康对照进行了比较。在目前的研究中，miR-146a 和 miR-155 的表达水平使用定量实时 PCR 在 15 名 CIS 患者和 61 名复发缓解型多发性硬化症 (RRMS) 患者以及作为对照的 32 名健康患者的血液样本中进行评估。此外，还评估了与患者临床病理变量的任何关联。仅在 RRMS 对照组的 miR-146a 和 miR-155 表达中发现失调。当对 RRMS 患者的性别特征、年发病率、诊断年龄、随访时间和使用的免疫调节治疗进行评估时，未观察到显着差异。然而，在维生素 D 水平、EDSS 值和攻击次数中的 miRNA 表达中发现了显着的失调。ROC曲线分析显示miR-146a和miR-155在RRMS-Control组的曲线下面积（AUC）显着。miR-146a 可能与维生素 D 缺乏和疾病残疾有关，而 miR-155 可能与发作次数有关。