Department of Medical Biochemistry and Microbiology, Uppsala University BMC Box 582, Uppsala, Sweden.
INSERM U974, CNRS UMR 7215, Institut de Myologie, UPMC Univ Paris 6 Paris, France.
Ann Clin Transl Neurol. 2014 Jan;1(1):49-58. doi: 10.1002/acn3.24. Epub 2013 Dec 30.
Myasthenia gravis (MG) is a chronic autoimmune disorder where autoantibodies target the nicotinic acetylcholine receptors (AChR+) in about 85% of cases, in which the thymus is considered to play a pathogenic role. As there are no reliable biomarkers to monitor disease status in MG, we analyzed circulating miRNAs in sera of MG patients to find disease-specific miRNAs.
Overall, 168 miRNAs were analyzed in serum samples from four AChR+ MG patients and four healthy controls using Exiqon Focus miRNA polymerase chain reaction (PCR) Panel I + II. Specific accumulation pattern of 13 miRNAs from the discovery set was subsequently investigated in the sera of 16 AChR+ MG patients and 16 healthy controls. All patients were without immunosuppressive treatment. Selected specific miRNAs were further analyzed in the serum of nine MG patients before and after thymectomy to assess the effect of thymus removal on the accumulation of the candidate miRNAs in patient sera.
Three miRNAs were specifically dysregulated in AChR+ MG patient sera samples. Hsa-miR150-5p, which induces T-cell differentiation, as well as hsa-miR21-5p, a regulator of Th1 versus Th2 cell responses, were specifically elevated in MG sera. Additionally, hsa-miR27a-3p, involved in natural killer (NK) cell cytotoxicity, was decreased in MG. Hsa-miR150-5p levels had the highest association with MG and were significantly reduced after thymus removal in correlation with disease improvement.
WE PROPOSE THAT THE VALIDATED MIRNAS: hsa-miR150-5p, hsa-miR21-5p, and hsa-miR27a-3p can serve as novel serum biomarkers in AChR+ MG. Hsa-miR-150-5p could be a helpful marker to monitor disease severity.
重症肌无力（MG）是一种慢性自身免疫性疾病，其中约 85%的病例自身抗体针对烟碱型乙酰胆碱受体（AChR+），胸腺被认为在发病中起作用。由于目前没有可靠的生物标志物来监测 MG 的疾病状态，我们分析了 MG 患者血清中的循环 miRNA，以寻找疾病特异性 miRNA。
总体而言，使用 Exiqon Focus miRNA 聚合酶链反应（PCR）Panel I+II 分析了来自 4 名 AChR+MG 患者和 4 名健康对照者的血清中的 168 个 miRNA。随后，在 16 名 AChR+MG 患者和 16 名健康对照者的血清中研究了发现组中 13 个 miRNA 的特定积累模式。所有患者均未接受免疫抑制治疗。选择的特异性 miRNA 进一步在 9 名 MG 患者的术前和术后血清中进行分析，以评估胸腺切除对候选 miRNA 在患者血清中积累的影响。
在 AChR+MG 患者血清样本中，有 3 个 miRNA 特异性失调。诱导 T 细胞分化的 hsa-miR150-5p 以及调节 Th1 与 Th2 细胞反应的 hsa-miR21-5p 在 MG 血清中特异性升高。此外，参与自然杀伤（NK）细胞细胞毒性的 hsa-miR27a-3p 在 MG 中降低。hsa-miR150-5p 水平与 MG 的相关性最高，并且在与疾病改善相关的胸腺切除后显著降低。
我们提出验证的 miRNAs：hsa-miR150-5p、hsa-miR21-5p 和 hsa-miR27a-3p 可作为 AChR+MG 的新型血清生物标志物。hsa-miR-150-5p 可能是一种有助于监测疾病严重程度的标记物。
