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Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human M.E. /CFS 2019

Discussion in 'BioMedical ME/CFS Research' started by Sly Saint, Nov 21, 2019.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/ chronic fatigue syndrome

    AkikoEguchi,SanaeFukuda,HirohikoKuratsunede,JunzoNojimag,YasuhitoNakatomi,YasuyoshiWatanabee,Ariel E.Feldstein
    https://www.sciencedirect.com/science/article/pii/S0889159119307627
     
    Last edited by a moderator: Nov 21, 2019
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  2. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Wow... probably a pretty significant paper... identified what’s in the EV’s.
     
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  3. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    This is the “something in the blood” @Simon M


    ETA: changed "what's" to "something"
     
    Last edited: Nov 21, 2019
  4. duncan

    duncan Senior Member (Voting Rights)

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    One of the authors is named Fukuda? Oh, sweet irony....
     
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  5. strategist

    strategist Senior Member (Voting Rights)

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    Maybe!
     
  6. Andy

    Andy Committee Member & Outreach

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    Sadly not available via Scihub yet. Looks interesting but researchers from Japan don't have a great track record of using a decent selection criteria, although given they talk of also looking at idiopathic chronic fatigue it raises my hopes in that regard.
     
  7. Simon M

    Simon M Senior Member (Voting Rights)

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    Oh dear, another paper I'm going to have to read... (abstract)

    Background:
    This is the key point:
    From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection.
    Using sick controls helps to justify the biomarker claim that follows:
    In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers. Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS
    Though, of course, replication will be essential.

    And at some point, Maureen Hanson's group will be reporting on their EV findings - so good to have independent groups working on the same issue (co-incidentally, Hanson's group also will be replicating the Japanese groups PET/neuroinflammation work).

    Actins are proteins that are the main component of the cell's 'cytoskeleton'. This is a dynamic, 3D web of filaments that pervade the cell and, amongst other things, transport molecules (mitochondria etc) around the cell. It's everywhere but tends not to get much attention.

    Video
     
    Last edited: Nov 21, 2019
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  8. Sarah94

    Sarah94 Senior Member (Voting Rights)

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    Well, it might be.
     
  9. Sarah94

    Sarah94 Senior Member (Voting Rights)

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  10. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    The full article does not appear to be online with the journal.

    I think I will wait to see that.

    I am sceptical about a claimed test that identifies 90-94% of PWME. Usually good diagnostic tests looking at potential causal mediators start out with a very low rate (<5%) in normals and maybe 20-40% in the condition of interest, 60% if you are lucky. 90-94% looks like fitting the numbers backwards from measuring lots of things and picking the ones that fit the cohort. The abstract is not written in a way that makes it easy to evaluate.

    The correlation with CRP is a bit peculiar since CRP is on average normal in ME.
     
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  11. Marky

    Marky Senior Member (Voting Rights)

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    I thought that was weird too

    Guess we have to wait for the paper!
     
  12. MerryB

    MerryB Established Member (Voting Rights)

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    The full paper is up now - just read it!
     
  13. wastwater

    wastwater Senior Member (Voting Rights)

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    Is there a link
     
  14. MerryB

    MerryB Established Member (Voting Rights)

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  15. Kitty

    Kitty Senior Member (Voting Rights)

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  16. Londinium

    Londinium Senior Member (Voting Rights)

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    Interesting. Looks like their initial result was sufficiently interesting that they recruited a validation cohort, if I’m reading this right.
     
  17. Hutan

    Hutan Moderator Staff Member

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    The finding of increased extracellular vesicles in people with ME/CFS looks pretty solid for the population they were sampling in. I can't comment on the methodology and the version of the report I'm looking at doesn't have the figures and tables.

    Sample 1 - 33 healthy controls; 39 people with Fukuda ME/CFS.
    # of EVs was higher in ME/CFS P=0.001

    Sample 2 - another 30 people with Fukuda ME/CFS.
    #of EVs was higher in ME/CFS (presumably compared to Sample 1 HCs). P=0.001
    They also note that the ME/CFS #EVs of Sample 1 was 'similar' to that of Sample 2.
    Sample 3? - 20 healthy controls; 30 people with Fukuda ME/CFS.
    Me/CFS # EVs also significantly higher. P=0.001
    (The way it is written suggests to me that the 30 ME/CFS were in addition to those of Sample 2)
    Supplementary Fig 1B hopefully makes it clear. Edit: in the methods they talk about 99 ME/CFS patients in the study, so it seems likely there were those 3 separate samples.

    Edit - it is later noted that the number of EVs was not significantly different between people with depression (8), ME/CFS (99) or idiopathic chronic fatigue (6).
     
    Last edited: Nov 22, 2019
  18. Hutan

    Hutan Moderator Staff Member

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    They found a correlation between CRP and # of EVs.
    They noted that this correlation was true even with data points within the normal range for CRP.

    They comment that CRP is a marker known to be increased in ME/CFS, quoting Fukuda 2016
    Fukuda, S., Nojima, J., Motoki, Y., Yamaguti, K., Nakatomi, Y., Okawa, N., Fujiwara, K., Watanabe, Y., Kuratsune, H., 2016. A potential biomarker for fatigue: Oxidative stress and anti- oxidative activity. Biological psychology 118, 88-93.

    I haven't heard this talked of elsewhere, in fact I thought I had heard the opposite, that CRP is not different. And I keep an eye on that, because my CRP levels have been consistently moderately elevated since becoming ill. I wonder if there is anything different between the Japanese ME/CFS population sampled here and ME/CFS populations elsewhere.
     
    Last edited: Nov 22, 2019
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  19. Hutan

    Hutan Moderator Staff Member

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    In contrast to the #EV study, the determination of what is in the EVs was much more of a pilot study.

    They purified EVs from the plasma of 3 healthy controls and 3 PwME. There were 124 proteins identified overall, with a number of proteins only in PwME or only in HCs. 75 of the proteins were significantly different in PwME compared to healthy controls - which is quite remarkable given the small sample size. I don't know if they accounted for multiple comparisons in that, probably not.

    They identified specific pathways that the proteins that were significantly different seemed to be relevant to:

    Then they analysed the contents of EVs for 4 PwME, 4 with depression and 4 with idiopathic chronic fatigue.
    they used a different process for concentrating the EVs I think, I'm not sure what impact this had, but this time a total of 579 proteins were identified.
    At this point I was despairing slightly, over the size of the EV characterisation samples and so on. But this point was encouraging:
    So they seemed to find the same differences between PwME and (depression and ICF) as they had found between PwME and healthy controls.
    These quotes are the guts of it:
    Where it says '12 most abundant proteins in the EVs' - I assume they mean, of the 31 proteins identified as significantly different. Table 1 has this data, so it would be worth looking to see exactly how they chose those 12.
     
    Last edited: Nov 22, 2019
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  20. Hutan

    Hutan Moderator Staff Member

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    So, looks like early days to me. I'm not going to spend time googling actinin etc at this point. I think Maureen Hanson's team is working on EVs, it will be interesting to see what they come up with.

    Where to start with the suggestion that the fact that GET helps people with ME/CFS indicates there is a muscle damage problem. :banghead:

    Hmm

    Before I finish up, I just want to comment on this:
    What a weird three symptoms to pick to characterise ME/CFS. Depression? I don't know where they are getting that from.
     
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