Different Exosomal microRNA Profile in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders
Different Exosomal microRNA Profile in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders
复制标题
Aquaporin-4 抗体阳性视神经脊髓炎谱系疾病中不同的外泌体 microRNA 谱。
DOI：
10.3389/fimmu.2020.01064
复制
发表时间：
2020-05-29
影响因子：
7.3
通讯作者：
Qiu, Wei
中科院分区：
文献类型：
--
作者：
Chen, Chen;Wu, Yunting;Qiu, Wei
神经瘤谱谱障碍（NMOSD）和多发性硬化症（MS）是中枢神经系统的炎症性脱髓鞘疾病。外泌体microRNA（miRNA）是脱髓鞘疾病的新兴生物标志物。在这项研究中，包括52名Aquaporin-4抗体血清阳性NMOSD患者，18种复发性多发性硬化症（RRMS）患者和17个健康对照（HCS）（HCS）进行下一代测序（NGS）。为了验证NGS结果，选择有价值的miRNA通过另一组患者的实时定量聚合酶链反应验证，包括31例NMOSD患者和14个HCS。此外，这些miRNA在一项纵向研究中也得到了验证。 NGS数据显示，NMOSD患者的外泌体miRNA谱与HCS不同。在可以区分NMOSD状态的那些潜在外泌体miRNA中，HSA-MIR-122-3P和HSA-MIR-200A-5P是最丰富的miRNA。此外，与汇出NMOSD相比，HSA-MIR-122-3P和HSA-MIR-200A-5P在复发NMOSD的血清外表体中显着上调。 HSA-MIR-122-3P和HSA-MIR-200A-5P与NMOSD患者的疾病严重程度有正相关。基因和基因组途径分析的京都百科全书表明，MAPK，WNT和RAS信号通路富集。进一步的生物学功能分析表明，这两个miRNA可能与NMOSD发病机理的免疫调节有关。我们的结果表明，外泌体传递的miRNA可以用作NMOSD的潜在生物标志物。
Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are inflammatory demyelinating diseases of the central nervous system. Exosomal microRNAs (miRNAs) are emerging biomarkers for demyelinating diseases. In this study, 52 aquaporin-4 antibody serum-positive NMOSD patients, 18 relapsing-remitting multiple sclerosis (RRMS) patients and 17 healthy controls (HCs) were included for the next-generation sequencing (NGS). To validate the NGS results, the valuable miRNAs were selected for validation by real-time quantitative polymerase chain reaction in another cohort of patients, comprising 31 NMOSD patients and 14 HCs. In addition, these miRNAs were also validated in a longitudinal study. NGS data revealed the exosomal miRNAs profile in NMOSD patients was different from HCs. Among those potential exosomal miRNAs which can distinguish NMOSD status, hsa-miR-122-3p and hsa-miR-200a-5p were the most abundant miRNAs. In addition, hsa-miR-122-3p and hsa-miR-200a-5p were significantly upregulated in the serum exosome of relapsing NMOSD compared with that in remitting NMOSD. Hsa-miR-122-3p and hsa-miR-200a-5p had positive correlations with disease severity in NMOSD patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the MAPK, Wnt and Ras signaling pathways were enriched. Further biological function analysis demonstrated that these two miRNAs might be involved in the immunoregulation of NMOSD pathogenesis. Our results indicated that miRNAs delivered by exosomes could be applied as potential biomarkers for NMOSD.