Researchers from the Center for Enervating Neuroimmune Disease have published a new study investigating extracellular vesicle (EV) proteins in ME/CFS. The research, published in Clinical and Translational Medicine, represents an important analysis of blood-derived EVs and their potential role in ME/CFS.

The study, led by Center Investigators Katherine Glass and Ludovic Giloteaux, analyzed plasma samples from 10 male ME/CFS patients and 12 age- and BMI-matched healthy sedentary male controls before, 15 minutes after, and 24 hours after a maximal exercise challenge, and is an extension of a prior study in an all-female cohort.

The researchers identified significant differences in EV protein cargo between ME/CFS patients and healthy controls at baseline. However, EV protein profiles in ME/CFS patients and controls showed the most pronounced differences 15 minutes post-exercise. ME/CFS subjects’ showed reduced EV protein levels related to energy metabolism, including the TCA cycle; immune overactivation, particularly in the complement system; and disruptions in protein homeostasis. Strikingly, changes in proteins involved in the endoplasmic reticulum (ER) stress response during the 24 hour recovery phase strongly correlated with post-exertional malaise (PEM) severity. We also observed dysregulation in protein homeostasis and ER stress response proteins in the female study. Notably, while EV protein dynamics in healthy controls correlated with exercise physiology metrics like VO₂ peak and ventilatory anaerobic threshold, these associations were absent in ME/CFS patients, suggesting a disruption in EV-mediated physiological adaptation. Together, these findings provide molecular insight into the mechanisms driving symptom exacerbation after exertion in ME/CFS.

This open access study, which represents an important step forward in understanding the molecular basis of ME/CFS, is freely available to read. The findings advance our understanding of how extracellular vesicles, important cellular messengers, may contribute to disease mechanisms in ME/CFS and suggest new directions for future research into diagnostic biomarkers and therapeutic targets.

To promote scientific collaboration and data transparency, the complete protein abundance data for each protein and subject has been made available through mapMECFS.