miRNA profiling of circulating EVs in (ME/CFS), 2018, Almenar-Pérez et al

Andy · Feb 3, 2019

Abstract only, or it's a poster presentation?

Background: ME/CFS (ICD-10; G93.3) is a complex multisystem disease of unknown origin with characteristic clinical features that include post-exertional malaise, cognitive dysfunction, orthostatic intolerance, on-going 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 toa lack of understanding of the underlying mechanisms of disease onsetand 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 down-regulation 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 EVmiRNA 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).
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https://search.proquest.com/openvie...f68f104f30/1?pq-origsite=gscholar&cbl=2030046

Trish · Feb 4, 2019

It's in the Journal of Extracellular Vesicles supplement and is described as a Document preview.
It looks like a follow up to this paper last year which was a pilot study that looked at extracellular vesicles in blood and found slightly more of them and they were significantly smaller in pwME. It was a small pilot study.

The one on this thread is about the downregulation of miRNA's in EV's and PBMC's. (I say that as if I know what I'm talking about!).

Looks like an area that needs lots more research and might prove significant.

wigglethemouse · Feb 3, 2019

Trish said: ↑

Looks like an area that needs lots more research and might prove significant.
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Dr. Maureen Hanson is also looking at EV's as part of her NIH center grant.

The second project, led by Hanson, will compare the content of extracellular vesicles between individuals with ME/CFS and controls. Extracellular vesicles are membrane-surrounded structures that contain cargos of proteins, lipids, hormones and RNAs that can influence the functions of cells when they fuse with them. These vesicles are known to be released after exercise and could be involved in cell-to-cell signaling. Hanson and colleagues will examine the proteins, small molecules and RNA content of extracellular vesicles before and after exercise, to see if inflammatory signals from the vesicles could be contributing to disease symptoms.
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Link : http://news.cornell.edu/stories/2017/09/94m-nih-grant-funds-chronic-fatigue-syndrome-center

Andy · Feb 3, 2019

One of the authors of this is from Hanson's team, Lubov Nathanson.

wigglethemouse · Feb 3, 2019

Andy said: ↑

One of the authors of this is from Hanson's team, Lubov Nathanson.
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Lubov Nathanson is shown in the PDF as belonging to NOVA. That would be Klimas's team.

boolybooly · Feb 4, 2019

So thinking out loud does this follow from previous miRNA / NK & CD8(+)T cell studies of Marshall-Gradisnik & Staines et al ?

2012
https://www.researchgate.net/public...nic_Fatigue_SyndromeMyalgic_Encephalomyelitis

The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required.
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2014
https://www.researchgate.net/public...nic_Fatigue_SyndromeMyalgic_Encephalomyelitis

Conclusion Our study is the first to identify circulating miRNAs from CFS/ME patients and also to confirm three differentially expressed circulating miRNAs in CFS/ME patients, providing a basis for further study to find useful CFS/ME biomarkers.
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(As an aside, its good practice to spell out acronyms at least once in any document using them. In this case EV presumably means Extracellular Vesicles, but the same abbreviation is also used to mean EnteroVirus so it could be confusing.)

Trish · Feb 4, 2019

boolybooly said: ↑

(As an aside, its good practice to spell out acronyms at least once in any document using them. In this case EV presumably means Extracellular Vesicles, but the same abbreviation is also used to mean EnteroVirus so it could be confusing.)
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I agree, though in this case the abstract is in the Journal of Extracellular Vesicles, so I guess they could reasonably assume their readers knew what they meant by EV.

shak8 · Feb 4, 2019

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miRNA profiling of circulating EVs in (ME/CFS), 2018, Almenar-Pérez et al

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