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Activin B is a novel biomarker for chronic CFS/ME diagnosis

Discussion in 'Latest ME/CFS Research' started by Kati, Mar 16, 2017.

  1. Kati

    Kati Patient in training

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    Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study

    Brett A. Lidbury, Badina Kita, Donald P. Lewis, Susan Hayward, Helen Ludlow, Mark P. Hedger and David M. de Kretser

    Journal of Translational Medicine201715:60

    Received: 11 January 2017
    Accepted: 10 March 2017
    Published: 16 March 2017

    Abstract

    Background

    Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available.

    Methods

    A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18–65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals.

    Results

    Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma
    .

    Conclusion
    Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

    Keywords
    Myalgic encephalomyelitis (ME) Chronic fatigue syndrome (CFS) Biomarker Activins Diagnosis
     
    leokitten, Mel9, L'engle and 29 others like this.
  2. Alvin2

    Alvin2 If humans were rational...

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    There have been many biomarkers shown in studies to be unique in ME/CFS, what will it take for one of them (hopefully the best one) to go mainstream and be available at doctor's offices?
     
    justy, L'engle, Jan and 2 others like this.
  3. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    From the article:
    [...]
     
    Last edited: Mar 17, 2017
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  4. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    https://en.wikipedia.org/wiki/Follistatin
    https://content.tigerfitness.com/follistatin-344-build-muscle/
    Umm, ok.:(

    https://racehorsemeds.com/product/follistatin-injection/
     
    Last edited: Mar 16, 2017
    Mel9, L'engle, slysaint and 3 others like this.
  5. Kati

    Kati Patient in training

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    "Competing interests:
    DdK is a founder of Paranta Biosciences, a company developing follistatin for clinical use, and a shareholder in the company, with a patent 2014366827 licensed to Paranta Biosciences Ltd"

    (Just saying) it may or may not be relevant. The study needs to be replicated with larger samples.
     
  6. Alvin2

    Alvin2 If humans were rational...

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  7. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    Supplement of the Month: MHP MYO-X
    http://www.muscleandfitness.com/supplements/build-muscle/supplement-month-mhp-myo-x
    "Click to buy" link on the above page above leads to a 404 error page.

    https://proteinfactory.com/follistatin/
    At the bottom of the page when you click on the picture of the box of MHP MYO-X, it takes you to an Amazon page with the following description:


     
    Last edited: Mar 17, 2017
  8. alex3619

    alex3619 Senior Member

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    There are steps required, such as calculation of specificity and sensitivity, including a study to find those, plus extra validating studies.

    Companies can market tests but in the US they will be blocked by the FDA unless they meet specific data requirements such as the above. I suspect many can move overseas, market the test, and get data to establish a history, but nobody has done this yet, with the exception of the approval of Ampligen in Argentina.

    All other biomarkers have not proven reliable enough to date.

    Once one biomarker is validated then we have a reference standard to compare other biomarkers to. It will also give a clue as to pathophysiology and causation.
     
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  9. alex3619

    alex3619 Senior Member

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    I have yet to read anything definitive but Activin B may have some role in B cell proliferation and destruction of actin fibers in cells. It does accelerate wound healing, but can lead to scarring. I have more reading to do.
     
    Last edited: Mar 17, 2017
    justy, Mel9, L'engle and 6 others like this.
  10. Alvin2

    Alvin2 If humans were rational...

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    fair enough, but with antipathy towards ME/CFS and lack of research money how are any test going to get through this process
     
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  11. alex3619

    alex3619 Senior Member

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    This appears to be pharma related. Sometimes that means deep pockets or at least the ability to raise funds. However I think many promising leads have failed to be followed through because of lack of funds. The existence of an expensive potential drug therapy also boosts chances of pharma funding.

    This is best viewed as a pilot study. Often this means they have more data to back their grant applications.
     
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  12. Alvin2

    Alvin2 If humans were rational...

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    i don't think the antipathy is pharma related. That said if a mechanism\ is discovered by OMF and a pharma company thinks its profitable to develop a drug then they will spend money to do so. However that has little to do with my original query.
     
  13. Hutan

    Hutan Senior Member

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    http://joe.endocrinology-journals.org/content/202/1/1.full.pdf
    The biology of activin: recent advances in structure, regulation and function
    Yin Xia and Alan L Schneyer1

    (note the b cells being talked about here are pancreatic beta cells; activin BKO mice are Activin B knock out mice, they don't have activin B)

    @JaimeS - you had some interest in insulin lately?

     
    JaimeS, J.G, Valentijn and 5 others like this.
  14. alex3619

    alex3619 Senior Member

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    This is Australian research, uses the 2003 CCC criteria, but only had 45 patients.
     
    Mel9 likes this.
  15. nandixon

    nandixon Senior Member

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    This looks promising. When they compared the ME/CFS patients to their larger “normal reference population,” i.e., 141 healthy volunteers, they found that not only was activin B higher in ME/CFS, but additionally:

    (my bold)

    The recent Fluge & Mella study strongly suggested that mTOR (mTORC1) is under-activated in ME/CFS, and Ron Davis confirmed that he believes mTOR is playing an important role.

    Critically, mTORC1 is a master controller of follistatin production:

    (my bold)

    So a major question is (assuming this study's results are confirmed in a larger cohort), what commonality could be causing both the increased production of activin B and the under-activation of mTORC1 (and hence the decreased follistatin) in ME/CFS?
     
  16. Alvin2

    Alvin2 If humans were rational...

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    i think you should ask Ron Davis this.
     
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  17. A.B.

    A.B. Senior Member

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    Nice find. It all seems to come down to some problem in the low level machinery controlling cellular metabolism.
     
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  18. Murph

    Murph :)

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    Another Aussie study! yay!

    However, is a bit under powered on the control side. They aimed to recruit 45 controls and only got 17. (How hard is it to get a few more people to give blood?!)

    Anyway I'm pleased they have population reference data to compare the CFS cohort to and reveal real differences. Our activin b levels seem to be really high, and the difference is big. Screen Shot 2017-03-17 at 6.08.41 PM.png

    The really exciting news is this:

    "to date, activin B levels have not been reported to be elevated or reduced in other diseases."

    might this be the great white whale? the unique biomarker? Only replication will tell.
     
    Last edited: Mar 17, 2017
    GodGenghis, Mel9, L'engle and 14 others like this.
  19. Hutan

    Hutan Senior Member

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    I think they probably have - this for example:
    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111276


    Hypoxia-inducible factors
    (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment

    HIF-1, when stabilized by hypoxic conditions, upregulates several genes to promote survival in low-oxygen conditions. These include glycolysis enzymes, which allow ATP synthesis in an oxygen-independent manner, and vascular endothelial growth factor (VEGF), which promotes angiogenesis.

    Could the raised levels of activin B in people with ME be a result of the some of the symptoms we may experience - POTS, hypoperfusion of our brains, gut ischaemia after eating, circulatory issues causing numbness and pins and needles?

    And perhaps it's a good thing.

    http://onlinelibrary.wiley.com/stor...3m&s=97cf88c7469eb808ea00b4804da69affd2325374
    The neuroprotective effect of Activin A and B: implication for neurodegenerative diseases

    It would be interesting to see some more measurement of activin A and B and follistatin in people with ME, with MS, brain injury and POTS, amongst others.
     
  20. A.B.

    A.B. Senior Member

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    mTOR reacts to environmental cues such as nutrients and oxygen supply, and adjusts cellular metabolism accordingly.

    Endothelial dysfunction has been reported in ME/CFS. If I understand it right, this could be an upstream source of poor oxygen supply, which then causes the various changes in metabolism and the difficulties meeting high energy demands that would result in PEM.

    However that seems at odds with there being something in the serum that is sufficient to cause problems. Maybe my mental model is just shoddy.
     
    Last edited: Mar 17, 2017
    Mel9, J.G, ScottTriGuy and 2 others like this.

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