Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/ chronic fatigue syndrome, by Akiko Eguchi, Sanae Fukuda, Hirohiko Kuratsune, Junzo Nojima, Yasuhito Nakatomi, Yasuyoshi Watanabe, Ariel E Feldstein, in Brain, Behavior, and Immunity November 2019 []



  • Circulating EV number was increased in ME/CFS patients correlating to CRP and BAP.
  • AUROC for circulating EVs was 0.802 allowing correct diagnosis in 90–94% of ME/CFS.
  • Proteins in actin skeletal regulation and EB virus infection were identified in ME/CFS patients.
  • Talin-1, filamin-A and 14-3-3 proteins were the most abundant proteins representing highly specific ME/CFS.

Research 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.

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