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Cytokine expression provides clues to the pathophysiology of Gulf War illness and ME

Discussion in 'Latest ME/CFS Research' started by snowathlete, Dec 17, 2014.

  1. snowathlete

    snowathlete

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    New paper from De Meirleir and the WPI.
    http://www.ncbi.nlm.nih.gov/pubmed/25514671

    Abstract
    Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current reports suggest that as many as 200,000 veterans who served in the 1990-1991 Persian Gulf War were afflicted. Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can consistently delineate the disease has not been defined. Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME. To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as healthy controls. Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of 92.5% and 64.9%, respectively. The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with respect to cytokine expression, GWI cases resemble control subjects to a greater extent than ME cases across a number of parameters. These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further suggest that the two diseases have distinct immune profiles despite their overlapping symptomology.
     
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  2. Sidereal

    Sidereal Senior Member

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    So hard to know what to make of these cytokine studies. They all seem to get different results.
     
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  3. cigana

    cigana Senior Member

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    The authors have concluded they are useful for identifying subgroups, rather than clearly delineating diseases. They seem to think the broad term ME/CFS is not so useful:

     
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  4. jimells

    jimells Senior Member

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    It suggests to me they keep looking under the street light 'cause that's where the light is. From what little I know, my impression is these kind of studies are relatively easy, they just need to draw blood and process it. I've seen several posts here and there that suggest biopsy studies could be more useful, but it's much harder to get volunteers, and of course getting the sample is likely a lot more work.

    It's off topic, but I can't help thinking that urologists don't seem to have much trouble getting people to sign up for their favorite biopsy procedure...
     
  5. adreno

    adreno PR activist

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    How consistent are cytokine profiles? How stable are measured values over time?
     
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  6. lansbergen

    lansbergen Senior Member

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    You can only find that out by testing it many times and over a long period.
     
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  7. adreno

    adreno PR activist

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    I assume this is generally not done, in ME/CFS research? And if not, how valid are the findings?
     
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  8. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    The study is interesting in it's comparison of 'CFS' (ME) vs GWS.

    Historically, both GWS + CFS are said to by psychosomatic by British psychiatrists. Curiously, the British Army 'lost' vaccination records for soldiers who went onto develop GWS and more people developed GWS who weren't deployed than those that were. (But they had vaccines).

    Away from politics both CFS and GWS both are associated to unexplained deaths and cancer, especially GWS.

    If CFS and GWS were psychological, not only would cytokine expression (differing from depression)
    not occur, but one would expect a similar 'cytokine signature' in both CFS + GWS as nothing much would be occurring pathologically.

    So in my view, this is why this paper by De Meirleir et al has some merit as it delineates between
    CFS + GWS using potential biomarkers. Another paper that has managed to do this with CFS vs another similar 'controversial' condition is the 2011 Natelson et al study.

    Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrom
    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017287

    That study was useful to prove that people who've been 'treated' for Borrelia infection don't share the same
    abnormal proteins in their spinal cord (and thus neurology affecting proteins) as those diagnosed with CFS.
    If anything, that paper was most useful for the Lyme community, not CFS.

    With this recent CFS (ME) study, the obvious 'flaw' (like all that have come before) is it unfortunately fails to link to a pathogen. Having said that, it appears after this publication, the authors following paper will compare an inflammatory profile to controls in a relatively large double blinded study.

    If my prediction is correct, you could suggest it was important to get this paper 'out of the way' first. It needed
    to demonstrate (as others have in the past) that GWS differs from ME, before making certain future claims (such as pathogen association) to ME in the future when again associating ME to inflammatory profiles (prospective biomarkers).

    Other people here wisely mentioned the fact inflammatory profiles needs measuring over time.
    This is very true. One could easily dismiss study subjects were infected 'on the day' (with something), however you can counter act that by saying +90% sharing of inflammation markers would mean that +90% of study participants happened to be infected with harmless pathogens (e.g. common cold) all on the same day of the blood draw. Rather unlikely.

    I can think of CFS researchers that are already taking blood draws repeatedly overtime (as forum member adreno mentioned), however this is in a small number of people which negates most of the findings unfortunately if one is going to get excited about the findings being definitive.

    Jarred Younger – Daily fluctuations in cytokines in CFS/ME
    https://www.masscfids.org/resource-...s-in-clinical-care-and-translational-research

    We have also seen this year, one can differentiate between how severely CFS/ME suffers are affected by measuring cytokines:

    Serum cytokines in patients with moderate and severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
    http://www.sciencedirect.com/science/article/pii/S1043466614002919

    If in the following years ME (as a subset of CFS) can hopefully come out of the closet as the dreadful disease that destroys lives, and once we have evidence of immune activation/inflammation that is consistent that differs from controls (by associating inflammation to infection), then I believe the idea of spending $600 on a CFS suffer to do a PCR for a suspected infection won't seem OTT. It may even become standard practice in those with CFS with signs of low grade chronic infection, who launch a weak immune response, and so remain chronically infected and further disabled. (That's unnecessarily disabled because these patients aren't given tests due to the disbelief of the authenticity of their suffering).

    Maybe novel cytokine expression matching accepted infections/autoimmune disorders in ME (CFS)will be another shove in the right direction into the infection and immunity camp for ME (CFS). I don't want to get too excited about De Meirleir et al's next paper, because unless a pathogen is named, one can easily dismiss the findings as non specific and this leaves the door open for hypothesizing about genes/stress, which further delays research and treatment.

    What we need desperately is someone to say to the research community, look here everyone. The majority of these people with this label ME (CFS) who meet or exceed CDC criteria, have this certain bug, and we can detect an inflammatory profile in practically all of them, in a double blind manner, in which the results are not shared by healthy controls. Can others do this? If so, are they CDC criteria/Canadian Criteria? Severely affected or moderate?

    That could really move the game forward, because by using inflammatory markers alongside a pathogen, the psych industry cannot just select 100+ psych patients and say ''we can't find the bug''. That won't wash, because those psych patients won't have the same inflammatory profile (as it's caused by the bug, or autoimmune activity caused by the bug) and not by being misdiagnosed with ME using Oxford criteria CFS, aka, UK PACE trial.
     
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  9. alex3619

    alex3619 Senior Member

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    Klimas is doing a lot of similar research, and is advancing to testing drug therapies in GWI, but cannot do the same for ME as there is not nearly as much funding.
     
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  10. snowathlete

    snowathlete

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    That's interesting. You know where there is more info on these two things?
     
  11. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    USA:

    In 2007, a Veterans Affairs report set off an alarm after it found that 73,846 Gulf War veterans had died, including 17,847 veterans who were deployed and 55,999 who did not deploy.
    Source:http://www.military.com/daily-news/2014/04/21/gulf-war-illness-thousands-still-report-symptoms.html


    USA:

    A former epidemiologist for the Department of Veterans’ Affairs told lawmakers on Wednesday that the agency’s Office of Public Health buries or obscures research findings on veterans exposed to environmental toxins and hazards going as far back as the Persian Gulf War. Steven Coughlin, who had worked more than four years for the VA before quitting over “serious ethical concerns” in December, said in testimony that leadership in the agency’s public health office did not want to find or reveal evidence that Gulf War illness and other sicknesses were linked to troops’ military experience. "On the rare occasions when embarrassing study results are released, data are manipulated to make them unintelligible,” he told the House Subcommittee on Oversight and Investigations. Coughlin said his former office never released findings of a $10 million study that produced data on 60,000 Iraq and Afghan war vets – of which up to 30 percent were Gulf War vets – that revealed exposures to pesticides, oil well fires and more. He said the results of a congressionally mandated study on Gulf War veterans and their family members also was never released, and claims he was advised that “these results have been permanently lost.”

    Source: http://m.military.com/daily-news/2013/03/14/whistleblower-va-hiding-veteran-health-data.html


    UK:

    2012:
    MoD tells Gulf War veteran his army medical records have been lost
    Source: http://www.birminghammail.co.uk/news/local-news/mod-tells-gulf-war-veteran-230442


    UK: 1999

    Fresh calls for Gulf War Syndrome inquiry
    "Certainly there were denials that there was a problem, there were denials about the use of organophosphates and certainly then, when there was some acceptance that people were falling ill, the tracing of medical records and the details of those records were just non-existent."
    Source: http://news.bbc.co.uk/1/hi/uk/507414.stm


    USA:

    ''But one problem that Sanders and others who served from 1987 to 1992 face is a lack of medical records. Working through the office of U.S. Rep. David Davis, R-1st District, Sanders was able to get copies of his military entry and exit physical exams. Everything else, including the record of his anthrax and other vaccines received while in service, are gone. He said a VA official once told him they were “inadvertently destroyed.”

    In a nutshell, Washington, D.C.-based Veterans Affairs spokesman Jim Benson and Northern Virginia-based Department of Defense spokesman Terry Jones said veterans seeking full VA health care must show their injury, illness or disability is connected to their military service. They said the letters of support can help Sanders.
    However, Benson and Jones also said they were not aware of a mass loss or destroying of records from the Gulf War era, although Sanders said they have been told by VA officials and others that medical records went missing for many who served in the Gulf War''.

    Source: http://www.vaccinetruth.org/new_page_7.htm


    "In the early months of 1994, staff of the Senate Committee on Veterans' Affairs interviewed 146 Persian Gulf War veterans... The respondents complained about numerous negative side effects of the vaccines and pills... One claimed that two people in his unit had heart attacks after taking [the experimental drugs] and that one died. There were numerous complaints about the quality of care and the lack of compassion of VA physicians and nurses. This included a doctor's comment claiming that the Persian Gulf War 'wasn't a real war' and a patient's complaint that a doctor told her that she was fine, after using a stethoscope that he had forgotten to put in his ears."(116)

    "Seven months of medical records are missing."
    "Asked for my medical record and was told all had been disposed of."
    "Medical record is lost forever."
    "20 years of medical records are now mysteriously gone."
    "All our medical records were destroyed.
    "
    "Doctors refused to put vaccinations in my medical record."
    "Was told my leave would be held up if I wanted copies of my medical record."
    "My medical record says my illness is not related to Agent Orange. This VA doctor has the wrong war!"

    Source: http://thinktwice.com/gulfwar.htm


    USA:

    A survey conducted with veterans by the committee determined that out of 150 Gulf War veterans interviewed:

    48 [32%] of them reported inaccurate medical records.
    28 [19%] of them reported missing or lost medical records.
    A total of 76 [51%] with missing or inaccurate medical records

    Source: http://www.gulfwarvets.com/ijom.htm cites Ibid., p.47
     
    Last edited: Dec 17, 2014
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  12. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    So it wouldn't surprise me that a combination of experimental vaccines and also troops on the batttlefield evaporating Saddam's cache of (American sourced) biological weapons and inhaling these agents in dust particles potentially caused strange diseases that were then passed on when returned home. (Wives seem to develop 'CFS' after sexual contact with GWS soldiers and also have a higher number of birth defects in babies). This may correlate potentially with some horrible 'germ' they acquired, such as weaponised Brucellosis or the myriad of germs America gave Saddam to defeat Iran.

    Or.... the soldiers share the ME pathogen from birth, but were given a toxic cocktail of drugs (antI nerve agents) that gave them a novel form of ME. This seems more likely. Think of a hypothesis where non aware folk with HIV are soldiers who are yet to develop symptoms, but are given a cocktail of experimental vaccines. 'Their' resulting AIDS, could be much different that conventional AIDS. ME isn't AIDS, but it may share a co-pathogen. Does that co-pathogen freak out when it comes into contact with pesticides and cause autoimmune disease? We don't know.

    It's odd how many people claim to have come down with ME around the same time of the Gulf War, and non deployed soldiers still developed GWS. How did they develop GWS if they never suffered 'battle stress'? The only link is vaccine and personal contact with people who did come back from the war (s).

    Or both scenarios.

    Factor in is a certain British psychiatrist (employed by the British Army) made both ME CFS and GWS his pet study and made his career on selecting both conditions, by denying they have a single cause to them at the same or similar time in history.

    A strange coincidence.

    If HERV's are proven pathogenic, it would make sense both GWS and subsets of CFS are autoimmune in nature, and this may explain the cytokine expression, and differing expression in various papers published.
     
    Last edited: Dec 17, 2014
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  13. Guzz

    Guzz

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    I am a little curious about this: is there some easy way to find all the cytokine studies you mention? Would be interresting to have a look at them. In ths case, I found the number of cytokines measured (77) quite high, but maybe that has been done before, too? And as others here have mentioned: if WPI and De Meirleir are on their way to identify more homogenous subgrups within this diverse patient "crowd", that seems like one of my dreams are about to come true?
     
  14. alex3619

    alex3619 Senior Member

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    One thing that is coming up is that ME and GWI, and from the above abstract, it looks like GWI and ME have different cytokine expressions. Similar syndrome, different chemistry. However the more we learn about either, the more we will understand the other.
     
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  15. Sidereal

    Sidereal Senior Member

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    Finding the abstracts would be relatively easy by doing a Pubmed search but I imagine many of the papers would be behind a paywall.
     
  16. wastwater

    wastwater Senior Member

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    Research1st Wrong war correct agent?
    I wonder if it could be something like dioxin,I think they poison the mitochondria
     
    Last edited: May 21, 2015
  17. student

    student Senior Member

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    Yes ist is this groop of organic chlor: (in Wood protections): PCP, Lindan, DDT, Dioxin, PCAD, PCSD … they stay in fatty cells. They change Transcription of Enzymes.

    Cholestrol-binders (citrus pectin), FIR sauna -Fett reduction, perhabs horsetail (Silizium) as well as Glutathion strengthening. Start low and slow (with impaired - Phase 1 / and phase II reaction) with Methylation (or Glutathion) support.
    There is alsways a need - To trick out fatty resorption of Gallblader cycles.. Before full excretion can be seen.

    Some (like PCAD, PCSD ) seem to dominate more the Lymph and Throat (lymphatic ring) detox mechanisms
     
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