Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome
Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome
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DOI：
10.1016/j.bbi.2019.11.015
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发表时间：
2020-02-01
影响因子：
15.1
通讯作者：
Feldstein, Ariel E.
中科院分区：
文献类型：
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作者：
Eguchi, Akiko;Fukuda, Sanae;Feldstein, Ariel E.
肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种严重的、令人衰弱的疾病，具有广泛的症状，包括疼痛、抑郁和神经认知恶化。全世界有1700多万人患有ME/CFS，主要是女性，发病高峰期为30-50岁。鉴于ME/CFS症状的广谱和病因不明，缺乏用于ME/CFS诊断和分层的特定生物标志物。在这里，我们展示了循环细胞外小泡(EVS)中的肌动蛋白网络蛋白为ME/CFS提供了特异的非侵入性生物标志物。我们发现ME/CFS患者的循环EVS显著增加，与C-反应蛋白和生物抗氧化潜能相关。循环EVS的受试者工作特征曲线下面积为0.80，可使90-94%的ME/CFS病例得到正确诊断。来自ME/CFS、健康对照组、特发性慢性疲劳和抑郁症的循环EV的两个独立的蛋白质组分析表明，ME/CFS患者的蛋白质参与了局部黏附、肌动蛋白骨架调节、PI3K-Akt信号通路和Epstein-Barr病毒感染。其中Talin-1、细丝蛋白A和14-3-3家族蛋白含量最高，代表了高度特异的ME/CFS生物标志物。我们的结果确定循环EV数和EV特异性蛋白是诊断ME/CFS的新的生物标志物，为ME/CFS的发病机制提供了重要的信息。
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, debilitating disorder with a wide spectrum of symptoms, including pain, depression, and neurocognitive deterioration. Over 17 million people around the world have ME/CFS, predominantly women with peak onset at 30-50 years. Given the wide spectrum of symptoms and unclear etiology, specific biomarkers for diagnosis and stratification of ME/CFS are lacking. Here we show that actin network proteins in circulating extracellular vesicles (EVs) offer specific non-invasive biomarkers for ME/CFS. We found that circulating EVs were significantly increased in ME/CFS patients correlating to C-reactive protein, as well as biological antioxidant potential. Area under the receiver operating characteristic curve for circulating EVs was 0.80, allowing correct diagnosis in 90-94% of ME/CFS cases. From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection. In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers. Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS.