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Analysis of Serum miRNA Profiles of Myasthenia Gravis Patients

机译:重症肌无力患者的血清miRNA谱分析

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摘要

Myasthenia gravis (MG) is an autoimmune disease characterized by the presence of autoantibodies, mainly against the acetylcholine receptor (AChR). The mechanisms triggering and maintaining this chronic disease are unknown. MiRNAs are regulatory molecules that play a key role in the immune system and are altered in many autoimmune diseases. The aim of this study was to evaluate miRNA profiles in serum of 61 AChR MG patients. We studied serum from patients with early onset MG (n = 22), late onset MG (n = 27) and thymoma (n = 12), to identify alterations in the specific subgroups. In a discovery cohort, we analysed 381 miRNA arrays from 5 patients from each subgroup, and 5 healthy controls. The 15 patients had not received any treatment. We found 32 miRNAs in different levels in MG and analysed 8 of these in a validation cohort that included 46 of the MG patients. MiR15b, miR122, miR-140-3p, miR185, miR192, miR20b and miR-885-5p were in lower levels in MG patients than in controls. Our study suggests that different clinical phenotypes in MG share common altered mechanisms in circulating miRNAs, with no additional contribution of the thymoma. MG treatment intervention does not modify the profile of these miRNAs. Novel insights into the pathogenesis of MG can be reached by the analysis of circulating miRNAs since some of these miRNAs have also been found low in MG peripheral mononuclear cells, and have targets with important roles in B cell survival and antibody production.
机译:重症肌无力(MG)是一种自身免疫性疾病,其特征是存在主要针对乙酰胆碱受体(AChR)的自身抗体。触发和维持这种慢性疾病的机制尚不清楚。 MiRNA是调节分子,在免疫系统中起关键作用,并在许多自身免疫性疾病中发生改变。这项研究的目的是评估61名AChR MG患者血清中的miRNA谱。我们研究了初发MG(n = 22),晚期MG(n = 27)和胸腺瘤(n = 12)患者的血清,以鉴定特定亚组的改变。在一个发现队列中,我们分析了来自每个亚组的5位患者和5位健康对照者的381个miRNA阵列。 15例患者未接受任何治疗。我们在MG中发现了32种不同水平的miRNA,并在包括46名MG患者的验证队列中分析了其中的8种。 MG患者的miR15b,miR122,miR-140-3p,miR185,miR192,miR20b和miR-885-5p的水平低于对照组。我们的研究表明,MG中不同的临床表型在循环miRNA中具有共同改变的机制,而胸腺瘤没有其他贡献。 MG治疗干预不会改变这些miRNA的概况。通过分析循环中的miRNA,可以找到有关MG发病机理的新见解,因为其中一些miRNA也被发现在MG外周单核细胞中较低,并且具有在B细胞存活和抗体产生中具有重要作用的靶标。

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