Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in ME/CFS, Almenar-Perez et al. 2020

Full Title:
Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

https://www.nature.com/articles/s41598-020-58506-5

 

Sample of 30 . 15 severe from biobank+15 controls

Great to see biobank fuelled work!

 

How are these findings related to the cytokine analysis of extracellular vesicles that Maureen Hanson presented at the 3rd OMF symposium last September? She hadn’t found any significant difference in the average size or concentration of total EVs in ME/CFS patients vs healthy controls, but different cytokine associations. I guess my question is, is there any link here?

Glad to see new findings about EVs and something that points towards exosomes!

Edit: Maureen Hanson’s presentation:

https://www.youtube.com/watch?v=2BZnL-ZKta4

she starts talking about EVs at the 9:50 ish mark.

Edit2: Some EV size and count differences:

 

I'm interested in their findings; however, I wonder if we would be better focusing on the GWAS study @Simon M has been involved in promoting. From memory a GWAS study may give us clues regarding causes. This study could potentially identify consequence e.g. if the small exosomes (increased in ME) come from a particular tissue --- then that might provide a clue to where to focus research. I suppose both have their place; however, considering these results are not remarkable, then I'd like the results of the GWAS study! E.g. I've been interested in a potential link to thyroid function in ME, a GWAS study might turn up something interesting regarding genes controlling thyroid function.


Some extracts from this paper
"lower levels for alkaline phosphatase and free thyroid hormone T4 levels"
"hormonal glands (mostly thyroid)"
"we find, following a database search formerly described by our group56, that hsa-miR-18a-5p can be upregulated by the anti-psychotic drug desipramine, while hsa-miR-146a-5p and hsa-miR-150-5p expression can be induced by morphine56, raising the possibility that the observed overexpression of these miRNAs derives from patient drug exposure and not from the disease itself. This highlights the enormous importance of detailed medication registry when studying molecular changes in these patients, as recommended by the ME/CFS NINDS CDEs46."

 

Summarising, searchable —

PBMCs
Over-expressed (p<0.05)

• miR-374a-5p
• miRNA-4516
• miR-340–5p
• miR-140-5p
• miR-18a-5p
• miR-146a-5p
• miR-106a-5p
• miR-17-5p
• miR-106b

p<0.1

• miR-21-5p

Under-expressed (p<0.05)

• miR-644a
• miR-451a
• miR-4454
• miR-7975
• miR-549a
• miR361-3p
• miR-1253
• miR-590-5p

EVs
Over-expressed (p<0.05)

• miR-4454
• miR-7975
• miR-150-5p
• miR-15a-5p
• let-7d-5p
• miR-423-5p
• miR-374a-5p
• miR-130a-3p

p<0.1

• miR-21-5p
• miR-320e
• miR-185-5p
• let-7g-5p
• miR-126-3p
• miR-223-3p
• miR-93-5p

Under-expressed (p<0.05)

• miR-183-3p
• miR-33a-5p

p<0.1

• miR-203a-5p
• miR-607
• miR-369-3p

Bold are miRs that are differentially expressed in both the PBMCs and EVs. Note that miR-4454 and miR-7975 are over-expressed in EVs but under-expressed in PBMCs. The paper says "At present, the significance of these differences is not understood." (I don't know if one possibility would be that PBMCs are off-loading those particular miRs via EVs.)

 

I don't know much about EVs and found this interesting. My immediate question was "Have mechanisms for selective sorting of microRNAs into EVs been described?"

Yes! They have. https://pubmed.ncbi.nlm.nih.gov/32331346/

 

Thanks! Will read. I had found these two to read as well —

MicroRNA sequence codes for small extracellular vesicle release and cellular retention (2021, Nature)
MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology (2022, Frontiers in Bioengineering and Biotechnology)