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Major Stanford Study Indicates Chronic Fatigue Syndrome (ME/CFS) is Inflammatory Disorder

There’s been a great deal of controversy and confusion surrounding ME/CFS — even whether it is an actual disease. Our findings show clearly that it’s an inflammatory disease and provide a solid basis for a diagnostic blood test.” Mark Davis

There’s nothing like a high-profile study from a major university. For one thing it can get you publication in one of the most prestigious journals around. The  journal the Montoya/Mark Davis study was published in, The Proceedings of the National Academy of the Sciences, is the official publication of the National Academy of Sciences. Its website gets about 21 million hits a month; this study is going to get around.

Dr. Jose Montoya, the leader of the Stanford Myalgic Encephalomyelitis/Chronic Fatigue (ME/CFS) Initiative  has been talking about this study for years. Now that it’s finally here, it’s making an impact with many media outlets picking it up.

The results were positive and that was good news indeed. This was one study we really didn’t want to fail.

Too Big To Fail?

Cytokine signature associated with disease severity in chronic fatigue syndrome patients Jose G. Montoya, Tyson H. Holmes, Jill N. Anderson, Holden T. Maecker, Yael Rosenberg-Hasson, Ian J. Valencia, Lily Chu, Jarred W. Younger, Cristina M. Tato, and Mark M. Davis.  Proc Natl Acad Sci U S A. 2017 Jul 31. pii: 201710519. doi: 10.1073/pnas.1710519114. [Epub ahead of print)

The study examined the levels of a very large number of cytokines (n=51) in the blood of a very large number of patients and healthy controls (ME/CFS=186; healthy controls= 388). Age, sex, race and something called “nonspecific binding” were accounted for.

missing the mark

This was one study we really didn’t want to fail

One of the biggest ME/CFS immune studies ever undertaken, done at a top University, this was a study that we dearly didn’t want to fail. This is the kind of study likely to be labeled “definitive”. It was on scale with the Columbia cytokine study, where co-authors Ian Lipkin and Mady Hornig analyzed 51 cytokines in 298 patients and 348 healthy controls.  If the results of these two hallmark studies were discordant, it would have had negative consequences to any immune interpretation of this disease.

Smaller cytokine studies in ME/CFS have a history of inconsistency, making the similarities in these two studies important.

Results

The first news was not good. The levels of only two cytokines, TGF-Î (elevated) and resistin (lowered) were different in the patients compared with controls.  Displaying an unusual level of consistency for ME/CFS, TGF-B has now been found elevated in about six out of the ten studies it’s been tested in.

TGF-B has not received a lot of attention possibly because researchers are not sure what it means. An anti-inflammatory cytokine that can have pro-inflammatory properties, the authors noted that TGF-B is elevated in a number of dissimilar conditions (cancer, liver disease, inflammatory bowel diseases among others). The authors suggested TGF-B may have pro-inflammatory properties in ME/CFS; instead of tamping down inflammation, they proposed it may be “may be a major factor in promoting relentless inflammation.”

Big Finding

“Remarkably, 17 cytokines were associated with severity in ME/CFS patients.” The study authors

Dr. Montoya got the money for the study and conceived it, and Mark Davis advised him on it, was the senior author of the paper, and tested the samples in his lab.

Davis has won a slew of prizes (The Paul Ehrlich Prize, The Gairdner Foundation Prize, The King Faisal Prize, the General Motors Alfred P. Sloan Prize) and is on the Open Medicine Foundation’s Scientific Board. He’s a big deal in the immune world.

bulls-eye

Montoya and Davis hit the bulls-eye when they threw severity into the mix

I talked to Davis a couple of days after the study’s publication.  I asked him about the main results; those 17 cytokines that predicted severity – was that a lot?  It’s an important question. A couple of cytokines popping out might mean that the immune system is involved but is not a major player – time to look someplace else.  A lot of cytokines showing up, on the other hand, suggests the immune system may very well be it in ME/CFS – time to dig deeper.

Was 17 cytokines a lot? Even in the staid language of scientific journals the surprise at the size of the effect came through: “Remarkably”, the paper said, “17 cytokines were associated with severity in ME/CFS patients.”

When I asked Davis if it was really a lot, I heard him take a deep breath:  “it’s a lot – really a lot” – he said. Getting a third of the immune factors to show up suggests massive immune involvement. Davis – who is involved in constructing immune signatures for different diseases and health – said everything he’s seen about this disease suggests autoimmunity.  That’s a particularly meaningful statement  from such a well-known immunologist. He’s getting to know ME/CFS pretty well: Montoya’s study is the biggest study his public lab has run.

(Mark Davis has two labs – his private research lab and a larger, more public lab he set up to run many more samples at a time. That lab, which got a big federal grant, was designed to bring the same kind of rigor he uses in his private lab to bigger studies.  Researchers like Dr. Montoya can bring their samples to the lab and have the lab test them. That’s what happened in this study)

A Different Kind of Disease?

Mark Davis thinks ME/CFS is probably an autoimmune disease. You don’t see the kind of overt cytokine increases in ME/CFS that are seen in autoimmune diseases like rheumatoid arthritis  and lupus.  This study, in fact, suggested that cytokines were not increased in the patient group as a whole relative to healthy controls.

Adding severity to the mix, however, suggested that cytokines were heavily involved in this disease. Mark Davis said he’d never seen a disease with mostly normal cytokine levels but which presented such clear indications that cytokines affected symptoms.  He suggested that other diseases like Alzheimer’s might display similar patterns if researchers started looking for them.

In an interview with Miriam Tucker, Dr. Montoya echoed the unusual nature of the disease: he simply called the immune activation in ME/CFS – as he has for some time now – a different kind of inflammation.

“Inflammation is much more complicated than two imperfect old measures [sed rate and C-reactive protein]. We’re showing an inflammation that has not been seen before.” Jose Montoya

Three Options?

But what could be causing this bizarre pattern?  Higher cytokine levels could certainly explain the more severe fatigue in some ME/CFS patients, but how do the low or normal cytokine levels explain the fatigue in the more moderately fatigued patients? They do have ME/CFS after all; even if they are less ill than the severely ill, they are still enormously fatigued but their cytokine levels aren’t elevated at all. In fact the cytokine levels are lower than normal in some of them. Three options have been suggested.

(1) Loss of Immune Control In the Severely Ill

One possibility the paper presented is that the healthier patients with lower levels of pro-inflammatory cytokines are able to control them to some extent. Their immune systems are grinding away but they’re keeping – probably at some cost – the pro-inflammatory elements under control. The control mechanisms of the sicker patients, though, have collapsed – they’re bearing the burden of unremitting cytokine activity.

(2) A Localized Infection

In conversation Mark Davis suggested that a localized infection could also be causing the immune system to react – not with the huge increases in cytokines seen in systemic inflammatory or autoimmune diseases but with small, harder to detect ones.  He’s not the first to suggest that. A couple of years ago Michael Van Elzakker proposed exactly that scenario for ME/CFS.

Different

ME/CFS may be a different kind of inflammatory disorder

Van Elzakker proposed that localized infections – probably involving the vagus nerve – were causing small, hard to detect elevations of cytokines. Meanwhile the infections were playing havoc with the vagus nerve’s ability to communicate sensory and immune information to the brain.

I asked Van Elzakker about the study.  He believes the cytokines this study picked up in ME/CFS are probably spillovers from an infection or injury. He cited Robert Dantzer, an important figure in sickness behavior research and pyschoneuroimmunology, who in a (2014) Trends in Neurosciences review, The Neuroimmune Basis of Fatigue agreed that with regard to fatigue:

 “The measurement of circulating concentrations of cytokines represents the main limitation of the present studies on fatigue and inflammation. Given that cytokines are autocrine and paracrine communication factors, their circulating levels have little functional value and represent mostly spillover from the site of cytokine production and action.

Given how profoundly limited many people with ME/CFS are – Van Elzakker believes these localized infections probably exist in the neuroimmune nerves such as the vagus or trigeminal nerves.

(3) Context  – Is Context King?

There’s another possibility. Gordon Broderick’s modeling work in chronic fatigue syndrome (ME/CFS) suggests that context may be king in the immune system.   During a recent phone call Broderick described the co-expression study he did that found a changed immune landscape in ME/CFS.  Cytokines such as IL-1b, 2, 4, IFN-γ, TNF-α  and IL-10 had larger than expected impacts in ME/CFS patients relative to healthy controls while other cytokines had less impact.

If Broderick’s right, none of the cytokines found in Montoya’s study need to be elevated to have a significant effect – they simply have to be embedded in a dysregulated immune network.

Leptin is Back

This is the second time leptin has shown up in a Stanford study, and the researchers suggested that it might be the keeping the chronic inflammatory state in ME/CFS intact. It turns out that adipokines – cytokines secreted by fat cells – like leptin may be able to trigger neuroinflammation. They’re also found in higher levels in women and may be a particularly important trigger in female dominated inflammatory diseases such as multiple sclerosis.

 Duration

In contrast to the Lipkin/Hornig and another study, this study found little evidence of increased cytokine levels earlier in the disease or decreased levels later in the disease. The small numbers of short duration patients (n=30) in the study, however, could have prevented any findings from reaching statistical significance. Interestingly, the study did not find that disease duration was correlated with severity; i.e. patients who had been ill longer were not necessarily worse off.

 Diagnostic Test?

Mark Davis suggested the findings might prove the basis for a diagnostic test but in conversation indicated we’re far from one right now. Much more study is needed.

The diagnostic test problem is greater in the low to moderately ill patients who have similar cytokine levels to healthy controls. How to devise a test to distinguish them from the healthy controls with similar cytokine levels is the big question.

Montoya reported that his team was working on a five-cytokine panel that would require a doctor first classifying each patient by severity. If Montoya can devise specific cytokine signatures for each level of severity, a test might be feasible, but it’s clearly going to be a complex undertaking.

Big Study (Too Big?)

Montoya rather courageously put a lot money into an area of research – cytokine analyses – that have had their problems in ME/CFS. As the Lipkin/Hornig study and this study showed, when it comes to immune studies size is definitely better.

While it is possible that this study had more controls than needed, at least Montoya didn’t err on the other side – too few patients; that might have been fatal to this study. Mark Davis thought that given all the noise in the data, that a smaller study might not have found much.

 Don’t Think Too Much: the Zen of ME/CFS

In a kind of Zen-like statement Mark Davis cautioned about “thinking too much” about this disease at this point.  Davis wasn’t suggesting not inquiring about the disease, but not coming to conclusions about it.  We’re not there yet. We’re more in a space of creative inquiry than anything else.

tea-house-mt-fuji

Mark Davis warned against coming to conclusions; more views of ME/CFS is what we really need

Things got even more zen-like when Davis referred to a famous series of paintings called Thirty-six views of Mt. Fuji to underscore where we are with ME/CFS right now. The celebrated series by Japanese artist Hokusai shows Mt Fuji from different perspectives including from at dawn, from a window in a house, from behind a huge wave, etc., etc.

To Davis, ME/CFS is like Mt Fuji; we need to look at it from a lot more angles to fully understand it. The most important thing we can do now is to test, test, test and let the data guide us.

This study may demonstrate that more than anything. It, after all, had four highly unusual results – very little evidence of immune dysregulation compared to healthy controls; massive evidence (17 cytokines!) on the other hand, that the immune system is effecting severity, a substantial number (on the other, other hand) of individuals with low or low-normal cytokine levels, and finally two cytokines with abnormal levels which didn’t have anything to do with severity at all.

This study, then, boosted interest in the immune system in ME/CFS, while raising a lot of questions about it at the same time. A lot of work – a lot of exploratory work –  remains to be done to figure this puzzle box of a disease out.

In fact, exploration is largely carrying the day in ME/CFS research. Montoya got hundreds of samples, tested them as widely as possible, analyzed them a bit and then stood back. Ditto with the Ian Lipkin/Mady Hornig immune study,  the metabolomics studies from Armstrong and Naviaux, (Naviaux, however, has a hypothesis), Ron Davis and the Open Medicine Foundation with their severe ME/CFS Big Data study, and Avindra Nath and his deep Intramural NIH study.  They’re all exploring.

Mark Davis’ talk at Open Medicine Symposium on Saturday should be a good one.  NINDS Director Dr. Koroshetz talked up Davis’s exciting findings in the recent NIH Telebriefing, and Ron Davis thinks they may be even more significant than this paper. If you’re at the Symposium you can ask him about his work or Mt Fuji or just say hello and thanks.

Treatment

This study is a major legitimizer and a big spur for more immune studies – particularly big immune studies. One thing it doesn’t present are clear treatment options. When I asked Mark Davis about treatment options, he was unwilling to commit to any line of treatment based on the results. He agreed that basing treatment options off of this study would be like shooting fish in a barrel.

That doesn’t mean the study won’t help on the treatment end. The severity results, after all, scream inflammation. That suggests anti-inflammatories might very well help. Ron Davis noted that many immune affecting drugs are under development right now which might be useful for ME/CFS in the future. We simply need more study to assess which targets might be best.

If Gordon Broderick’s right, though, it may take more than knowing a cytokine’s levels to find the right target. Broderick’s working on complicated models that incorporate the effects hormone levels, in particular sex hormone levels, have on immune factors in ME/CFS.  Broderick believes he’ll be able to devise a treatment approach that pushes the immune system one way and then another in order to nudge it back to a stable and healthy state.

Fatigue or Functioning?

While the multi-dimensional fatigue index used to assess fatigue has been validated as a good measure of fatigue across many diseases, one wonders if a functionality scale might have worked better. Fatigue is what ME/CFS is known for, but it’s real impact is on functioning. It’s possible to be very fatigued and still work, or to be pacing effectively – and not doing much work – and be less fatigued.

The MFI worked well in this study and past ME/CFS studies have used it, but one wonders if a scale that tracks functionality – how much activity one is actually doing – might have been more effective at tracking severity.

 Slow Progress

Montoya has been given much (reportedly $8 million donation in 2008) and promised much, but the ME/CFS work has been slow. He’s a toxoplasmosis expert, possibly the top expert in the country, and he’s been pouring out toxoplasma studies – fourteen since 2015 – but the work in ME/CFS has gone much slower.  Since 2009 he’s been the senior or lead author on just four ME/CFS studies – two of which involved the valganciclovir trial and predated the opening of his ME/CFS center.

This latest study was the most important one – it will undoubtedly help the field – but one hopes that with this monster study out of the way Montoya will be able to move faster on his other ones. His current research projects page lists ten studies. Two involve the Zinns who, unable to publish their work at Stanford, exited to work with Lenny Jason. Those studies are surely not extant.

The eight others, though, involve brain imaging, neuroendocrine, gene expression, cardiovascular, immune and pathogen studies. In a telephone conversation Mark Davis referred to some scintillating results he and Montoya are working on using the immune data Montoya gathered.  Let’s hope we’ll see those results and more from Montoya’s Chronic Fatigue Initiative in the not too distant future.

Conclusion

lighthouse

This study, as did the Lipkin/Hornig study, suggested you have to approach ME/CFS differently than other diseases to be successful.

One of the things that emerged from this study is that ME/CFS really, really is different and woe to any researcher who assumes that it’s not. The regular rules of the road do not apply – you can’t just measure cytokine levels and expect to get anything. You have to dig deeper, and what this study and the large Lipkin/Hornig study before it demonstrated was that if you do dig deeper, you might stumble on something extraordinary.

The study’s excellent pedigree – it’s size, the lab it took place in and the journal it was published in – guarantees it will get noticed and that’s a good thing. The most important aspect of the study may be the legitimization it confers on the illness. Hopefully the study will introduce new researchers intrigued by what could be a new type of inflammatory disorder to the field.  While more work is needed, the study also points to possible future effective treatment options. Lastly, the study indicates, as did the Lipkin/Hornig study, that bigger really is much, much better in ME/CFS research. Hopefully funders will take a cue from these large studies, and support the bigger and more definitive studies this disease needs to move forward.

 

 

 

 

 

 

 

 

 

 

 

 

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39 Comments

  • Pat

    August 11, 2017 at 1:16 am - Reply

    Great job Cort! Thank you. This is so encouraging.

  • aquafit

    August 11, 2017 at 2:07 am - Reply

    I cannot believe that that these researchers keep trying to prove their individual prior theories (Montoya infection and Broderick oxidative stress) in the face of overwhelming evidence that it is the immune system itself, aka, the connective tissue, which is the issue. **face palm**

    adipokines – well yes, of course! Adipose tissue is connective tissue. Adipose tissue stores ATP cells until we need to call them up to be used. Even Dr. Ron Davis said that mitochondria perform fine in the lab but they go wonky in the blood serum. Blood serum is liquid connective tissue.

    Alzheimers disease is recognized as being caused by lifetime or late life use of anti-cholinergic drugs. Seems as we lose collagen we are more prone to fossil fuel derived drugs crossing our blood brain barrier. That’s why geriatric patients have a low anti-cholinergic burden”.

    My theory is that those who have connective tissue issues (and there are hundreds as well as “undifferentiated”) may have a vulnerability, then when an infection comes along, meds send one off the deep end (even though they may kill the infection), something like Reye’s syndrome. For others, puberty, menses and menopause – times that require a lot of cell signalling within healthy collagen – or aging can be the trigger to problems. Or injury.

    • Philip Hayward

      August 11, 2017 at 6:35 am - Reply

      “…then when an infection comes along, meds send one off the deep end….”

      Very interesting hypothesis. In my case and others I know, could a giardia infection and the standard drug treatment for this, be the trigger?

  • Pati

    August 11, 2017 at 2:49 am - Reply

    Please keep us updated!

  • Guang Rong

    August 11, 2017 at 2:56 am - Reply

    I’m an ME patient and not sure if I’m encouraged by anything in this article. With all my due respect, to me, those medical scientists are just like blind men touching an elephant.

    • Cort Johnson

      August 11, 2017 at 3:12 pm - Reply

      The theme at the Workshop is basically we need more data – we need big studies by good researchers – like this one.

      • Feral Boy

        August 12, 2017 at 9:27 pm - Reply

        I think Guang Rong is expressing the frustration that many of us feel: there are many researchers collecting data in their fields of expertise – and this is, of course, important and necessary – but no one has yet connected the dots in such a way as to explain the pathogenesis, nor provided mechanisms to explain the many body systems involved, nor provided a useful strategy for ameliorating this condition. Even Komaroff writes, in his commentary, “Hopefully, a decade from now, “doctors will know better what to measure and, more importantly, what to do to ease the suffering caused by this illness.” A decade! Hopefully!

        Yes, there is immune dysfunction, and this study will help us understand it better. But others have found brain dysfunction, mitochondrial dysfunction, microbiota dysfunction, muscle dysfunction, collagen dysfunction, cardiac dysfunction, etc. It’s like the old chicken/egg paradox, multiplied a dozen times. And this study – to my addled brain, at least – just made the waters cloudier, and a cure seem further off in the distance.

        • Cort Johnson

          August 12, 2017 at 11:46 pm - Reply

          Well said.

  • Robert Tinti

    August 11, 2017 at 3:57 am - Reply

    This is great news. I feel stiff all the time. Is the comment above true about anti-cholinergic drugs and alzheimers? I’m starting to have a real problem with memory.

    • paminaforte

      August 11, 2017 at 9:52 pm - Reply

      You might want to look into ketamine infusion therapy, which appears to be pro-cholinergic. Though research has focused primarily on its use for depression and pain syndromes it has also shown promising results for CFS, Lyme and PTSD.

  • Robert Tinti

    August 11, 2017 at 3:58 am - Reply

    But I can’t sleep without them

  • Julie

    August 11, 2017 at 4:13 am - Reply

    It’s a step in the right direction. GREAT article, Cort.

  • Plum Blossom

    August 11, 2017 at 5:18 am - Reply

    A step in the right direction,so encouraging. I thank you Cort and your followers as I knew nothing about CFS/Fibromyalgia until I found this site.After a lifetime of being ignored I feel so much better just by having some knowledge. Take care.

    • Cort Johnson

      August 11, 2017 at 3:10 pm - Reply

      Glad it’s helping Plum…

  • Philip Hayward

    August 11, 2017 at 6:33 am - Reply

    Cort, could there be any relevance to this, in what “dejurgen” was saying on this thread about fibromyalgia?

    https://www.healthrising.org/blog/2017/07/10/immune-disease-low-dose-naltrexone-ldn-fibromyalgia-study-suggests-fm-inflammatory-side/

    There are 4 comments; the first three are what I am referring to. Dejurgen was discussing with me, potential reasons why “inflammation” seems to be not present in FM. If I understand correctly, it is possible that the immune system somehow disallows inflammation to occur because it would be so severe – it would be all over the body. Inflammation really should occur in response to the dysfunctions and toxicity in the muscle tissue / fascia – but it somehow does not occur. Its absence has led to a major wrong assumption on the part of many researchers, who like to disbelieve that there is pain there at all, because there is no inflammation.

  • Gail

    August 11, 2017 at 7:20 am - Reply

    Cort, do you know if the OMF is looking into something along the lines of Michael Van Elzakker’s Vagus Nerve theory?

    • Cort Johnson

      August 11, 2017 at 3:10 pm - Reply

      Not that I know of. I think they’re concentrating on Ron Davis’s energy experiments and with casting as wide a net as possible with their many studies.

  • Philip Brown

    August 11, 2017 at 8:56 am - Reply

    Well what a surprise. A group of researchers find that, after spending millions of dollars, they are no nearer to a cure, a treatment or even a diagnostic test. Their only conclusion is that more research is required. Please send your checks to http://www.completewasteoftime.com

  • Sarah R.

    August 11, 2017 at 2:54 pm - Reply

    Great to learn about this study and these results, Cort. Thank you so much for your ongoing and wide-ranging coverage of research into our diseases.

  • Kate

    August 11, 2017 at 7:04 pm - Reply

    “Remarkably, 17 cytokines were associated with severity in ME/CFS patients.”

    What do they mean ASSOCIATED. That is so vague. Were they proportional, more in quantity? Did severe patients have 17 and less severe patients have 9? This grand study finds a relationship between cytokines and severity but no one can specify what this relationship is? Then how did they know there was a relationship? What are they talking about?

    I tried to read the whole article but couldnt find what relationship they meant.

    • Cort Johnson

      August 11, 2017 at 7:19 pm - Reply

      From the abstract

      Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α.


      https://www.ncbi.nlm.nih.gov/pubmed/28760971

      This means that people with milder illnesses had lower levels of ALL these cytokines relative to the people with more severe illnesses.

      • Kate

        August 12, 2017 at 4:08 am - Reply

        Thanks, I did not understand the phrase “upward linear trend.” I appreciate so much that you answered. Sometimes I just can’t think.

    • NormLC

      August 12, 2017 at 2:57 am - Reply

      The researchers are exaggerating the significance of their results. Buried inside the text of the published study “these 17 cytokines did not distinguish cases from controls overall” and “the two cytokines that did distinguish cases from controls (*on average only*), TGF-β and resistin, did not exhibit a linear relationship with disease severity”.

      The range of the cytokine levels measured in patients actually overlap the same levels found in some of the healthy controls. These cytokine levels CANNOT be used to predict who is sick or how sick they are. Only by averaging the results can any claims be made about causation.

      This study is an example of how to make data fit a theory.

      • Cort Johnson

        August 12, 2017 at 9:13 pm - Reply

        We shall see. 17 cytokines associated with severity is a lot: a third of all cytokines measured. I think cytokines must affect severity and the rest is a mystery. Its certainly not a standard inflammatory disease.

      • Kate

        August 14, 2017 at 6:17 pm - Reply

        Now I am not sure this is true. Our beloved Jared Younger doing ME research in Birmingham Alabama is totally joyous at having found C-reactive protein (CRP) numbers that correlate with flares in PWME/CFS as shown over 30 days yet those CRP numbers would be considered NORMAL, not different from controls, as far as range goes.

        • NormLC

          August 14, 2017 at 11:43 pm - Reply

          The researchers already knew who was sick and who wasn’t, and then looked for a trend in the data to match the sickness. The values found in the “trend” in inflammatory markers are also found in people who are not sick.

          • Kate

            August 15, 2017 at 1:42 am -

            Are you saying this about Jared Youngr’s study. You are wanting me to derive a conclusion from what you write here. I don’t know what that conclusion would be. Are you doubting the value of Jared’s work? Why would he be so excited about it if it has no meaning?

  • Rain

    August 12, 2017 at 3:20 pm - Reply

    While I do agree that inflammation is a major symptom of M.E./CFS, Stanford University, as well as other noted Universities and scientists have acknowledged the the “cause” of the systemic symptoms pf this disease (including inflammation) stem from the oxidative stress it causes to the mitochondria directly. The antibodies this disease produces releases the B cells that attack the mitochondria. So I think labeling M.E./CFS as an inflammatory “disorder” is counterproductive because M.E./CFS is a disease that causes inflammation as a “symptom” but inflammation is not the true cause of this disease.

    The reason this concerns me is because science has taken so many twists and turns in labeling this disease that it has become an ongoing struggle to keep this disease within the parameters of it’s true nature and cause. The CDC has created such havoc with continually attempting to reclassify and rename M.E./CFS, trying to isolate it into a one symptoms disorder or devalue it into nothing at all that we can ill afford having to go down yet a another path of misinformation.

    • Kate

      August 13, 2017 at 4:47 am - Reply

      I agree. The idea that someone has found THE CAUSE is the one cause/one cure fallacy all over again. So, they’ve found cytokines that are wonky. Great. But then the usual overblown conclusions.

  • Gail

    August 14, 2017 at 1:51 am - Reply

    I can’t remember which speaker mentioned this, but at the OMF symposium yesterday, someone said that ME/CFS has a 100% overlap with Systemic Inflammatory Response Syndrome (Sepsis). Could we all have a low-level Sepsis?

  • Prashanti

    August 14, 2017 at 5:54 pm - Reply

    This is a little of topic, however, Stanford’s research for brain issues was mentioned. I tried to get in to it, but I was a couple of years too old. I was wondering if anyone knows what imagining techniques they are using in their research. I have not been able to get a response from Stanford.

  • Prashanti

    August 14, 2017 at 5:55 pm - Reply

    typo above…. I meant to write…This is a little off topic

  • Matthias

    August 15, 2017 at 8:30 am - Reply

    I wouldn’t say this study is a ‘waste of space’, but it’s not a game changer is it?
    I would also be reluctant to jump to conclusions.
    In terms of the cytokine – severity link, it could just as easily be correlation as causality.
    The study asks more questions than it answers.
    If I take myself, I have long term mild/moderate level CFS. What’s causing my fatigue? This study would suggest it is not cytokines, because the cytokines of the mild CFS patients was low compared to controls.
    Would hope for more, by now.

  • Matthias

    August 15, 2017 at 8:39 am - Reply

    One could posit from this study that something independent to the cytokines is causing CFS, but that that ‘something’ causing CFS results in higher cytokines for those with higher severity.

    My theory is that CFS is a result of faulty interaction between peripheral inflammation and the brain. The central problem is in the brain / CNS, but symptoms will be greater in patients with greater peripheral inflammation, as the faultiness is even more overrun when the peripheral inflammation is greater.

    • paminaforte

      August 15, 2017 at 2:19 pm - Reply

      A pattern of my symptoms appears consistent with the theory. I am in a later stage of post-viral CFS/ME and had begun to notice an association of brain symptoms and leg swelling increasing and decreasing at the same time (increased fatigue goes without saying). The increased leg swelling is especially curious in this context. (Later, now, it never goes away and other symptoms that used to come and go have become chronically worse also.)

      Most prominent other symptoms affect my central and peripheral nervous system, nerves, and muscles and tendons. New, unusual symptoms including subtle, odd signs of those began to accumulate following a very stressful medical procedure a couple decades ago, when exhaustion began to worsen and an autoimmune stress-triggering pattern was emerging. Signs of autoimmunity however did not show up in my blood work for another 12 years, by which time I had experienced a couple more severe and unusual infections, and stressful doctor interactions associated with serial misdiagnoses were becoming chronic.

      Since the worsening of my disease I have experienced benefit from only two incidental things: Following an EMG my symptoms improved for about 24 hours, and ketamine, administered for medical procedures on three occasions, had a dramatically transformative affect but was short-lived, lasting less than 3 weeks. I believe those 2 things offer clues to the nature of the disease for me and for many others of a similar profile.

  • Matthias

    August 15, 2017 at 8:41 am - Reply

    This study underpins my theory:

    http://www.natap.org/2009/HIV/031009_07.htm

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