Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

Myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS) is a serious disease whose cause has yet to be identified. Objective markers of the disease are also not well understood and would serve as important tools in diagnosis and management. One potential biomarker or transmitter of immune signals in ME/CFS is the extracellular vesicle (EV) compartment. These small, membrane bound particles have been shown to play a key role in intercellular signaling. Our laboratory has focused on methods of detection of EVS in clinical samples. In this study we explored whether the prevalence of EVs in the plasma of participants with mild or severe ME/CFS differed from the plasma of healthy control participants. By staining for multiple cell surface molecules, plasma EVs could be fingerprinted as to their cell of origin. Our study revealed a significant correlation between severe ME/CSF and levels of EVs bearing the B cell marker CD19 and the platelet marker CD41a, though these changes were not significant after correction for multiple comparisons. These findings point to potential dysregulation of B cell and platelet activation or homeostasis in ME/CFS, which warrants validation in a replication cohort and further exploration of potential mechanisms underlying the association.

Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro

“…Of the 12 analytes measured, no significant differences among the groups were found regarding the release of MMP-2 ( Figure 3 i), myoglobin, CRP or SAA (data not shown). Furthermore, given the divergent secretion profile of serum-treated HUVECs we reproduced the experiment with patient plasma-derived extracellular vesicles (EVs) which have been postulated to play an immunomodulatory role in ME/CFS patients [ 34 , 35 ].…”

The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…can adhere to the endothelial lining and play a part in the manifestation of ME/CFS symptoms, possibly by impairing oxygen and nutrient delivery to tissues [30]. More recently, platelet activity and markers have been implicated in ME/CFS, although the authors indicated a loss of significance after statistical corrections [31]. Endothelial abnormalities have also been noted [32,33].…”

Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses

“…The authors also alluded to the notion of anomalous clot deposition on the endothelium which can impair substance exchange between blood and tissues, and subsequently give rise to ME/CFS symptoms. Bonilla and colleagues determined that extracellular vesicles from ME/CFS patients contained significantly elevated levels of the platelet marker, CD41a [ 171 ]. CD41a is a component of GPIIb/IIIa complex – the platelet receptor that binds fibrinogen and von Willebrand factor, and mediates platelet adhesion and aggregation, and clotting.…”