Vesicles and Signaling

Probing the Pathophysiology of ME/CFS through Proteomics and Metabolomics

By analyzing metabolites, circulating inflammatory molecules, and extracellular vesicle (EV) cargo in blood and urine samples from before and after exercise sessions, we aim to uncover markers and mechanisms of post-exertional malaise in ME/CFS.  We have published our analyses of targeted plasma and urine metabolomics data acquired by Metabolon, Inc.1, 2  These studies reveal important differences in exercise response between ME/CFS subjects and controls.  Video presentations about the plasma metabolomic study can be found here and about the urine metabololomic study here.

Further analyses of metabolites from plasma obtained before and after exercise testing are ongoing in collaborator Frank Schroeder’s laboratory at the Boyce Thompson Institute.  His group uses untargeted mass spectrometry methods to identify metabolites.

Extracellular vesicles are additional important components of plasma that may play a role in ME/CFS.  EVs are released into the circulation during exercise and could therefore contain biomarkers or contain cargo that plays an active role in mediating the abnormal response to physical activity in ME/CFS.  EVs contain signaling molecules that can affect the functions of recipient cells.  We published a pilot study demonstrating that cytokine networks differ in EVs isolated from plasma from ME/CFS subjects and controls at baseline, without an exercise test.3

To study how EV composition, size, and number changes in response to exercise, we isolated them from subjects before a CPET, immediately after the CPET, and 24 hours later.  Proteins were isolated from samples from the three time points and characterized by mass spectrometry.  The extensive protein data is currently under analysis.

1. Glass KA, Germain A, Huang YV, Hanson MR. Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS PatientsInternational Journal of Molecular Sciences. 2023; 24(4):3685.

2. Germain A, Giloteaux L, Moore GE, Levine SM, Chia JK, Keller BA, Stevens J, Franconi CJ, Mao X, Shungu DC, Grimson A, Hanson MR. Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome. JCI Insight. 2022 May 9;7(9):e157621.

3. Giloteaux, L., O’Neal, A., Castro-Marrero, J. et al. Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study. Journal of Translational Medicine. 2020; 18, 387.

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