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Extracellular Vesicles in ME

Pyrrhus

Pyrrhus

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Well, 2020 brought us a lot of bad memories, but at least it also brought us a few ground-breaking studies on extracellular vesicles!

I thought I'd start a thread to collect together the various discussions on extracellular vesicles (EV) in ME. Hopefully this will aid in the comparison of studies. Please feel free to add more studies or discussions as needed.

What is an extracellular vesicle?
  • A "vesicle" is like a bubble. It is surrounded by a fatty membrane and is filled with water and other things.
  • An "extracellular vesicle" is any vesicle that is found in the body outside any cell.
  • An "exosome" is a special type of extracellular vesicle derived from a special process. (endocytic pathway)
  • Exosomes are typically of the size 30-150 nanometers, but other extracellular vesicles can be larger.
  • An extracellular vesicle can contain proteins, micro-RNA's, cytokines, viruses, and lots of other things.
  • Most studies that look at extracellular vesicles only look at the EV's in the blood.
@Murph provides much more detailed information about extracellular vesicles in this post:
https://forums.phoenixrising.me/thr...-known-as-stealth-spheres.75937/#post-2198325
 
Pyrrhus

Pyrrhus

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U.S., Earth
Circulating extracellular vesicles as potential biomarkers in CFS/ME: an exploratory pilot study (Castro-Marrero et al. 2018)
Discussion:
https://forums.phoenixrising.me/thr...s-in-cfs-me-an-exploratory-pilot-study.58966/
Main points:
  • The aim of this study was to isolate and characterise blood-derived EVs in ME.
  • Blood samples were collected from 10 Spanish ME patients and 5 matched healthy controls.
  • Patients appeared to have more EV's, but of a smaller size, than controls.
  • Patients had EV's of average size 140 nanometers, while controls had EV's of average size 210 nanometers.
 
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Pyrrhus

Pyrrhus

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U.S., Earth
Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human ME/CFS (Eguchi et al. 2020)
Discussion:
https://forums.phoenixrising.me/thr...s-as-blood-biomarkers-for-human-cfs-me.78410/
Main points:
  • This study looked at the proteins inside the EV's.
  • More EV's were found in patients than in controls.
  • Patients with higher markers of inflammation had even more EV's.
  • Talin-1, filamin-A and 14-3-3 proteins were the most abundant proteins correlated with ME/CFS.
  • The authors suggest that these results could be used as a biomarker for ME.
 
Pyrrhus

Pyrrhus

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Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in ME/CFS (Almenar-Perez et al. 2020)
Discussion:
https://forums.phoenixrising.me/thr...les-in-me-cfs-almenar-perez-et-al-2020.79140/
Main points:
  • This study looked at the micro-RNA's (miRNA) inside the EV's.
  • Micro-RNA's are normal RNA molecules that the cell makes to inhibit the production of certain proteins.
  • Although we don't yet understand the role of miRNA's that well, some researchers have found that certain miRNA's are correlated with certain diagnoses.
  • Blood samples of 15 severely affected ME patients and 15 healthy controls were obtained from the UK ME Biobank.
  • Patients appeared to have more EV's, but of a smaller size, than controls.
  • 10 miRNA’s in EV’s were significantly different in ME compared to controls.
  • The authors suggest that these results could be used as a biomarker for ME.
 
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Pyrrhus

Pyrrhus

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U.S., Earth
Cytokine profiling of extracellular vesicles isolated from plasma in ME/CFS: a pilot study (Giloteaux et al. 2020)
Discussion:
https://forums.phoenixrising.me/thr...cfs-a-pilot-study-giloteaux-et-al-2020.83183/
Main points:
  • This study looked at the cytokines inside the EV's.
  • They looked at EV's in 19 ME patients and 19 controls.
  • The average size of EV's did not differ between patients and controls.
  • However, ME patients had more EV's of size 30-130 nanometers than healthy controls.
  • Comparison of cytokine concentrations in EV's of patients and controls yielded no significant differences.
 
Pyrrhus

Pyrrhus

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A discussion about extracellular vesicles that contain viruses:
https://forums.phoenixrising.me/threads/viral-extracellular-vesicles-known-as-stealth-spheres.75937/
Main points:
  • Extracellular vesicles can contain viruses such as enterovirus, rotavirus, or norovirus.
  • One EV can contain many copies of a virus.
  • Transmitting viruses through EV's, instead of through individual viral particles, may lead to greater disease severity.
  • Viruses inside EV's are hidden from the immune system.
  • Transmitting viruses through EV's may not require any cell-entry receptors.
 
Pyrrhus

Pyrrhus

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New paper on Mitochondrial DNA in Exosomes:

Exosome-associated Mitochondrial DNA is Elevated in Patients with ME/CFS and Stimulates Human Cultured Microglia to Secrete IL-1β
https://www.researchsquare.com/article/rs-154011/v1 (not yet peer-reviewed)
Discussion here:
https://forums.phoenixrising.me/thr...an-cultured-microglia-to-secrete-il-1v.82835/
Main points:
  • The amount of mitochondrial DNA in exosomes from the blood of ME patients increases after exercise.
  • Protein content of exosomes was lower in ME patients compared to controls and was even lower after exercise.
  • It's not clear what their point was, but they said that the mitochondrial DNA caused pro-inflammatory macrophages to release the pro-inflammatory cytokine Interleukin 1 beta.
 
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W

Wishful

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If you've read the full paper, did it show that ME patients' mtDNA after exercise was higher than the controls? The abstract didn't make that clear. Maybe protein content is simply lower in all people who are 'ill'.
 
Pyrrhus

Pyrrhus

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Wishful said:
If you've read the full paper, did it show that ME patients' mtDNA after exercise was higher than the controls? The abstract didn't make that clear.
Click to expand...

I don't think they measured that. In fact, I don't think the controls were even subjected to an exercise challenge. They probably could have designed the clinical trial better, or at least explained their logic better. And remember, this paper has not yet been peer-reviewed.
 
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Pyrrhus

Pyrrhus

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Pyrrhus

Pyrrhus

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Messages
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Location
U.S., Earth
Diagnosis of ME/CFS With Partial Least Squares Discriminant Analysis: Relevance of Blood Extracellular Vesicles (González-Cebrián et al., 2022)
https://forums.phoenixrising.me/thr...nalysis-relevanc-gonzalez-cebrian-2022.87476/

From abstract:
Consul said:
A Partial Least Squares-Discriminant Analysis (PLS-DA) model initially based on 817 variables: two demographic, 34 blood analytic, 136 PBMC miRNAs, 639 Extracellular Vesicle (EV) miRNAs, and six EV features, selected an optimal number of five components, and a subset of 32 regressors showing statistically significant discriminant power. The presence of four EV-features (size and z-values of EVs prepared with or without proteinase K treatment) among the 32 regressors, suggested that blood vesicles carry relevant disease information.
Click to expand...

From author on Twitter:
We can separate severe ME/CFS patients from Healthy controls with 100% accuracy.
Click to expand...
 
W

Wishful

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That study on Proteomics uses Fukuda criteria for ME subjects (how many would qualify under better criteria?), and compares them against healthy controls. They really need to compare the results against similarly unhealthy non-ME controls.
 
C

Consul

Messages
600
Wishful said:
That study on Proteomics uses Fukuda criteria for ME subjects (how many would qualify under better criteria?), and compares them against healthy controls. They really need to compare the results against similarly unhealthy non-ME controls.
Click to expand...
They write about their criteria usage 2 places in this article i think. One place they say Fukuda and another place they say Canada and/or Fukuda. If the second mention is correct it still sounds like some of the patients may just have fukuda which i dont think is good enough for NIH funded research centers.
 
O

Osaca

Senior Member
Messages
344
Consul said:
They write about their criteria usage 2 places in this article i think. One place they say Fukuda and another place they say Canada and/or Fukuda. If the second mention is correct it still sounds like some of the patients may just have fukuda which i dont think is good enough for NIH funded research centers.
Click to expand...
Wow, Fukunda? That's shocking.
 
O

Osaca

Senior Member
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344
Not the best of news, but at least ok. Let's hope future studies with newer sample don't have these issues.

Screenshot 2023-05-14 at 12.11.20.png
 
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