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Brain Behav Immun. 2019 Nov 20. pii: S0889-1591(19)30762-7. doi: 10.1016/j.bbi.2019.11.015. [Epub ahead of print]

Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome.

Author information

1
Department of Gastroenterology and Hepatology, School of Medicine, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan; JST, PRETO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan; Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA 92093, USA. Electronic address: akieguchi@clin.medic.mie-u.ac.jp.
2
Department of Health Welfare Sciences, Kansai University of Welfare Sciences, Kashiwara 582-0026, Japan; Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan; RIKEN, Center for Biosystems Dynamics Research, Kobe 650-0047, Japan.
3
Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
4
Nakatomi Fatigue Care Clinic, Osaka 541-0043, Japan.
5
Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan; RIKEN, Center for Biosystems Dynamics Research, Kobe 650-0047, Japan; RIKEN Compass to Healthy Life Research Complex Program, Kobe 650-0047, Japan.
6
Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Abstract

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.

KEYWORDS:

Actin network proteins; Circulating EV; ME/CFS; Non-invasive biomarkers

PMID:
31759091
DOI:
10.1016/j.bbi.2019.11.015

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