miRNA profiling of circulating EVs in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) by Eloy Almenar-Pérez, Lubov Nathanson, Teresa Sánchez-Fito, Leonor Sarria, Germán Cerdá-Olmedo, Elisa Oltra in Journal of Extracellular Vesicles, suppl. Supplement 1; Abingdon Vol. 7, (2018): 139.
Research abstract:
Background:
ME/CFS (ICD-10; G93.3) is a complex multisystem disease of unknown origin with characteristic clinical features that include postexertional malaise, cognitive dysfunction, orthostatic intolerance, ongoing flu-like symptoms and unrefreshing sleep in conjunction with other. Its worldwide prevalence is 0.4%–1% with a female to male ratio of 6:1. Current treatments rely on the management of symptoms due to a lack of understanding of the underlying mechanisms of disease onset and progression. The aim of this work was to identify biomarkers of ME/CFS by analysing miRNA profiles of patient plasma EVs and comparing them to those of their PBMCs. This information should improve our knowledge of ME/CFS and allow the development of unbiased quantitative diagnostic methods.
Methods:
miRNA profiles of PBMCs or EVs isolated from plasma (Invitrogen cat.4484450) of ME/CFS patients and population, sex, age and BMI-matched healthy participants (N = 15 per group) from the ME UK Biobank (London, UK) were determined using Nanostring technology (nCounter Human v3 miRNA Expression Assay Kit).
Gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) were used to determine disrupted cellular functions in ME/CFS. The study was approved by the DGSP-CSISP CEIC (ref. UCV201701), Spain. Signed informed consent was required for inclusion of samples.
Results:
miRNA profiles evidenced a global trend for miRNA downregulation in patients with respect to healthy controls (76% and 64% of the miRNAs presented inhibition, by at least 50%, in PBMCs and EVs respectively; while only one miRNA in PBMCs and 6% of them in EVs showed upregulation to this level). Qualitatively, miRNA profiles in PBMCs did not match those obtained from EVs indicating active packaging of miRNAs in EVs. The functions to be affected by the deregulated miRNAs support a model of immune, mitochondrial and neural defects for this disorder.
Summary/Conclusion:
This is the first report of paired PBMCs and EV miRNA profiles of ME/CFS patients by enzyme-free array technology. The results confirm previous proposals that this epigenetic mechanism is linked to the pathophysiology of ME/CFS. Validation studies with expanded cohorts are needed before particular miRNA profiles can be used as biomarkers of ME/CFS in a clinical setting.
Funding: The study was funded by the ME Association’s Ramsay Research Fund (RRF) (UK).
