Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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DOI：
10.1038/s41598-020-58506-5
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发表时间：
2020-02-07
影响因子：
4.6
通讯作者：
Oltra, Elisa
中科院分区：
文献类型：
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作者：
Almenar-Perez, Eloy;Sarria, Leonor;Oltra, Elisa
肌痛性脑脊髓炎/慢性疲劳综合症 (ME/CFS) 是一种病因不明的使人衰弱的多系统疾病，影响着全世界数千人。其诊断仍然依赖于排除由于完全缺乏疾病特异性生物标志物而导致无法解释的疲劳的医疗问题。我们的团队和其他人探索了 microRNA 图谱 (miRNomes) 作为这种疾病诊断工具的潜在价值。然而，参与者的异质性、数量少、检测样本的多样性以及其他分析前变量阻碍了疾病相关 miRNome 的鉴定。在这项研究中，我们的团队首次评估了英国 ME 生物库中招募的重症患者的外周血单核细胞 (PBMC) 和细胞外囊泡 (EV) 中的 ME/CFS miRNomes，以使用标准操作程序 (SOP) 评估具有最佳诊断能力的血液成分，从而将基于 miR 的诊断方法快速转化为临床。我们的结果表明，常规肌酸激酶 (CK) 血液值、血浆 EV 物理特征（包括计数、大小和 zeta 电位）以及有限数量的差异表达 PBMC 和 EV miRNA 似乎与严重 ME/CFS 显着相关 (p < 0.05)。基因富集分析指出表观遗传和神经免疫失调途径，与之前的报告一致。批准通过仅限于这几个潜在区别变量的经济有效的方法进行群体验证。
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multisystemic disease of unknown etiology, affecting thousands of individuals worldwide. Its diagnosis still relies on ruling out medical problems leading to unexplained fatigue due to a complete lack of disease-specific biomarkers. Our group and others have explored the potential value of microRNA profiles (miRNomes) as diagnostic tools for this disease. However, heterogeneity of participants, low numbers, the variety of samples assayed, and other pre-analytical variables, have hampered the identification of disease-associated miRNomes. In this study, our team has evaluated, for the first time, ME/CFS miRNomes in peripheral blood mononuclear cells (PBMCs) and extracellular vesicles (EVs) from severely ill patients recruited at the monographic UK ME biobank to assess, using standard operating procedures (SOPs), blood fractions with optimal diagnostic power for a rapid translation of a miR-based diagnostic method into the clinic. Our results show that routine creatine kinase (CK) blood values, plasma EVs physical characteristics (including counts, size and zeta-potential), and a limited number of differentially expressed PBMC and EV miRNAs appear significantly associated with severe ME/CFS (p < 0.05). Gene enrichment analysis points to epigenetic and neuroimmune dysregulated pathways, in agreement with previous reports. Population validation by a cost-effective approach limited to these few potentially discriminating variables is granted.