The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelit

Discussion in 'Latest ME/CFS Research' started by Kati, Jun 1, 2015.

  1. Kati

    Kati Patient in training

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    Another paper from Sonya Marshall and team! open access

    http://www.biomedcentral.com/1471-2172/16/35

    Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

    Abstract
    Background
    Abnormal immune function is often an underlying component of illness pathophysiology and symptom presentation. Functional and phenotypic immune-related alterations may play a role in the obscure pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The objective of this study was to investigate the functional ability of innate and adaptive immune cells in moderate and severe CFS/ME patients. The 1994 Fukuda criteria for CFS/ME were used to define CFS/ME patients. CFS/ME participants were grouped based on illness severity with 15 moderately affected (moderate) and 12 severely affected (severe) CFS/ME patients who were age and sex matched with 18 healthy controls. Flow cytometric protocols were used for immunological analysis of dendritic cells, monocytes and neutrophil function as well as measures of lytic proteins and T, natural killer (NK) and B cell receptors.

    Results
    CFS/ME patients exhibited alterations in NK receptors and adhesion markers and receptors on CD4+T and CD8+T cells. Moderate CFS/ME patients had increased CD8+ CD45RA effector memory T cells, SLAM expression on NK cells, KIR2DL5+ on CD4+T cells and BTLA4+ on CD4+T central memory cells. Moderate CFS/ME patients also had reduced CD8+T central memory LFA-1, total CD8+T KLRG1, naïve CD4+T KLRG1 and CD56dimCD16− NK cell CD2+ and CD18+CD2+. Severe CFS/ME patients had increased CD18+CD11c− in the CD56dimCD16− NK cell phenotype and reduced NKp46 in CD56brightCD16dim NK cells.

    Conclusions
    This research accentuated the presence of immunological abnormalities in CFS/ME and highlighted the importance of assessing functional parameters of both innate and adaptive immune systems in the illness.


     
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  2. SOC

    SOC

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    Now if I only had a clue what all that means in terms of symptomology, functionality, and treatment. :whistle:

    It sounds like it ought to be useful to other researchers, at the very least, as well as providing evidence of clear immunological abnormalities to refute the annoyingly (and incorrectly) repeated, "There are no known abnormalities in ME/CFS."
     
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  3. Kati

    Kati Patient in training

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    They found differences between moderate and severe patients. For instance, with monocytes, there was a higher than control reading for the moderates and lower than control for severe patients.

    I am bothered by their use of the Fukuda criteria, it should be mandatory these days that all patients ate required to have post-exertional relapse feature in their disease. However they mentioned that no patients had a feature of 'sadness' (meaning they were not confused for depressed patients)
     
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  4. lastgasp

    lastgasp Guest

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    "Participants were then excluded if they were ... experiencing symptoms of CFS/ME that did not conform to the Fukuda criteria for CFS/ME"

    What?! This is crazy, that would mean most (if not all) severe pwME would be excluded - because we typically have 20 or more symptoms. Fukuda has 8 plus fatigue. It doesn't even include orthostatic intolerance for example.
     
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  5. Sidereal

    Sidereal Senior Member

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    Fukuda criteria are almost as bad as Oxford.
     
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  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Interesting that even if it isnt the best criteria, they are still finding alot of abnormalities and immune dysfunctions.
     
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  7. Kyla

    Kyla ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ

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    interestingly this also sounds like a definition of "Mild" and "Moderate" ME to me, as opposed to what they are calling "Moderate" and "Severe"

    "Moderate patients are mostly able to maintain normal daily activities but may be hampered by reduced mobility while severely affected CFS/ME patients experience high levels of daily fatigue and are typically housebound"
     
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  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Im not sure about this study but i know they were making provisions for severe bed bound patients to participate in their studies. I think they even have a medical ward set up for this. But dont quote me on this, i just temember reading something about this in griffith university cfsme news letter??
     
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  9. Scarecrow

    Scarecrow Revolting Peasant

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    It's poor characterisation in general. I suppose if 'normal daily activities' means basic personal grooming, light housework and some grocery shopping, provided the shops are close, moderate seems about right. Almost certainly not working or studying at any level.
     
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  10. Hutan

    Hutan Senior Member

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    I'm a bit surprised, given the March 2015 Hornig/Lipkin findings, that researchers haven't all hurried off to re-analyse their data before going to print - to take into account the variable of the number of years since illness onset. Perhaps there hasn't been enough time yet.

    Average time since illness onset was 6.5 years. That suggests that there could have quite easily been a mix of short and long periods since illness onset.

    And yes - Fukuda and the moderate/severe definitions. Seems like the NCNED team, for all of its enthusiastic work, could use a bit more input from a patient group.
     
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  11. SOC

    SOC

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    I agree. That's not moderate and severe by any standard I know. I expected better from this group, so I'm puzzled.
     
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  12. snowathlete

    snowathlete

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    This group clearly believes that the disease is not psychological. But they keep on using Fukuda, over and over again. It puzzles me too, and has for some time. I can understand using Fukuda in some instances, it may help get funding for instance, but not in isolation. Why not use Fukuda and one of the much better criteria, if you must still use Fukuda?

    This studies results, for instance, may have looked identical with CCC or different. But we simply cannot know because of this limitation.
     
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  13. Valentijn

    Valentijn Senior Member

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    My biggest concern in that they might be using Fukuda because they don't have enough CCC/ICC/SEID patients. If all patients (or enough for statistical analysis) met more stringent criteria, I would have expected them to say that in the paper.

    And while Fukuda might be a political necessity in the US to keep government funders happy, that would not apply to researchers in Australia.
     
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  14. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    These researchers have been working on cfs for a few years now and originally used fukuda. They had some good research publushed and i wonder if they were too far down the road with previous research using fukuda to then change. I just wonder if they changed to the CCC if this would have affected their previous results or hard to compare their previous research to current research if they changed criteria.

    would changing to the CCC make the research they have now done null and void?
     
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  15. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I suspect researchers would not receive funding if they did not use Fukuda. I haven't seen anyone really address this issue. Coercion at this level is pretty watertight and has long-term implications irrespective of advocate initiatives at other levels.

    In defense of the Griffith Uni folk, they have attempted to differentiate serious me/cfs in at least some of their studies within the restrictions of only being able to use Fukuda. I think they are aware of the issues but have their hands tied. They have very strong ties with CDC re funding.

    When you come down to it, this political wedging of CFS means that the only viable option is for patients to focus on ME as a separate serious illness, regardless of whether CFS and ME are the same.
     
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  16. SOC

    SOC

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    Yet researchers in the psychology/BPS field get funding when they use no established definition, just generalized fatigue. And to add insult to injury, they publish that their research is on ME/CFS, whether their cohort meets an accepted definition or not.
     
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  17. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    It does appear that the UK situation is so controlled by the psychology/BPS, there is no need for them to restrict studies to the US-based Fukuda definition.
     
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  18. alex3619

    alex3619 Senior Member

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    This seems to be a logical next step. I have been hoping future studies will do this. In order to see if they had enough time though, you have to look at the submission date, not the publication date, and then realize the paper was finalized some time earlier than that.
     
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  19. duncan

    duncan Senior Member

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    This embracing or earnestly trying to replicate the three-year split concerns me. I don't feel confident that it will get the logical nod it should.

    In the UK, for instance, the BPS school has home court advantage. They need give little more than a polite acknowledgement that Lipkin's effort even happened. After that, they can ignore it, or demand someone else replicate in a robust and substantive fashion - and then someone else again. Even after that, I suspect they'd find a way to spin.

    Look at what is going on in the Lyme wars with persisiters. Three independent efforts have demonstrated unequivocally that Bb cells survive IDSA-recommended treatments in vitro. Kim Lewis from NorthEastern U, Ying Zhang from Johns Hopkins, and Monica Embers from Tulane, each led teams that showed conventional abx were insufficient to eradicate all Bb cells. And, of course, all one needs for a disease to spread is one cell capable of cell division...

    This seems like a slam dunk. But the response from mainstream Lyme has been worse than cautious; it can be interpretive as almost dismissive. Their retort ,more or less,has been "Prove these claims in vivo. Prove persisters occur in infected patients."

    If that sounds fair, let me assure you, it is not. It is devilishly difficult - as in next to impossible - to find spirochetes in untreated Bb patients outside of an EM. After treatment, footprints will be vanishingly available. They know this. The best that can be done is to demonstrate with PCR, and that is woefully insensitive, and likely to miss infections.

    It would be just as fair to ask someone to prove the disease has been eradicated in a patient with elevated Bb titers- this cannot be done, either.

    Historically, claims that infringe on mainstream Lyme territory are either dismissed out of hand as meaningless, or hailed as unsubstantiated. Sometimes they are simply ignored. These strategies serve them well because of the nature of the disease.

    The same can be said about ME/CFS. The burden of proof may be foisted onto the shoulders of the interlopers. With phantom or stealth or undefined pathogens or mechanisms at play, and hostiles holding the high ground, even laurelled advocates like Lipkin - or Lewis - can find it hard to make individual steps translate into sustained gains.
     
    Last edited: Sep 12, 2015
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  20. leokitten

    leokitten Senior Member

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    Also the Hornig/Lipkin findings really need to be replicated and validated before being used as part of an experimental hypothesis. Cytokines are finicky things which make measuring them and interpreting the results very difficult.
     
    Kati likes this.

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