Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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New era for ME/CFS research as top cytokine study attracts media headlines

Discussion in 'Phoenix Rising Articles' started by Simon, Mar 5, 2015.

  1. Forbin

    Forbin Senior Member

    Just curious if anyone knows if the immune system could produce the kind of effect found in the paper if a toxin were involved instead of a pathogen. I don't know if it could do this, but if the immune system regarded a toxin as a pathogen it wouldn't be able to "kill it," so might it then stay in the "on" position in a futile effort to rid the body of it? Or is this just a looney idea?
    Last edited: Mar 6, 2015
    joe12 and oceiv like this.
  2. Simon


    Monmouth, UK
    Yes, graphic issue (made it smaller above)
    To my knowledge IFN-g is primarily anti-viral though I saw some papers found it promoted killing intracellular bacteria too. Sorry, no news re that pathogen results, which is odd as the first ones were reported in Sep 2013.
  3. Simon


    Monmouth, UK
    Dr Mady Hornig has been answering questions on Reddit (people vote on questions in advance, she answers the most p popular ones). Here are her answers relating to this study:

    • Prof_Mady_HornigProfessor|Columbia University|Mailman School of Public Health[S] 22 points an hour ago

      The inflammation of ME/CFS appears to give way, over time (in our analysis, >3 years), to what appears to be a pattern not dissimilar to premature aging of the immune system (“immune exhaustion” or “immunosenescence”). Typically, high levels of inflammation are associated with high rates of cardiovascular disease, through a process whereby inflammatory cytokines drive atherosclerosis and potentially myocardial infarctions (heart attacks). This does not seem to be the case in ME/CFS over time, at least not in the majority of patients. Thus, we believe that there is a much different process that is affecting the function of the immune system – and we’re working actively to understand that process. Why the immune system is so dysregulated must be understood.

      We have work coming out soon that focuses on spinal fluid cytokines. Stay tuned.
    • Prof_Mady_HornigProfessor|Columbia University|Mailman School of Public Health

      Our study found that cytokines differed for ME/CFS of short duration (</= 3 years) compared with ME/CFS of long duration (>3 years), as well as from healthy controls. This study, though large by ME/CFS research standards, was cross-sectional. Currently, we are generating data from a longitudinal study of ME/CFS, looking at how cytokines change over the course of a year or more, in relationship to changes in the clinical picture. We believe that these new data will give us a better glimpse of the mechanisms involved in these cytokine changes over the ME/CFS disease trajectory.
    Prof_Mady_HornigProfessor|Columbia University|Mailman School of Public Health

    The results of the rituximab studies have been intriguing. I consider them to be highly worthy of intensive follow up. Rituximab, a monoclonal antibody, depletes B cells through its binding to the CD20 receptor. We found evidence in our plasma cytokines study that cytokines produced by different types of B cells are altered differentially in the early vs late phases of ME/CFS. We envision that an even wider range of monoclonal antibodies, such as those directed against the inflammatory cytokine, IL-17A, may also potentially be of benefit for individuals with high plasma levels of that cytokine (largely short duration ME/CFS subjects).

    A study that would be particularly welcome, would be one that looked at the capacity of immune biomarkers to predict who might benefit from rituximab therapy. As with all such monoclonal antibody therapies, extreme caution is required to ensure safety of this type of treatment. Hopefully, the ongoing studies will also shed light on that issue. Who is the right candidate for such therapies? What are the risks?

    One final Q&A that people might find interesting
    Prof_Mady_HornigProfessor|Columbia University|Mailman School of Public Health

    I think that diseases that defy medical explanation will always be the ones at greatest risk of being maligned in this manner. Research that defines reliable biomarkers and that demonstrates treatment responses in blinded clinical trials, using hypothesis-driven interventions, can go a long way to overturning these entrenched assumptions. Of course, the best defense is to uncover the biological causes of ME/CFS. We are hopeful that an adequate funding stream for ME/CFS research will allow us to accelerate the process of finding the causes and discovering appropriate interventions for this disease.
    Kati, Mij, Sean and 3 others like this.
  4. Mij

    Mij Senior Member

    Dr. Bryon Hyde also discusses this:

    Non-Infectious M.E. Type Disease:
    I have not discussed noninfectious M.E.-type disease. Similar M.E. phenomena can occur due to diffuse CNS injuries from toxic chemical in jury. I have seen this in police officers who have fallen into toxic chemical ponds in pursuit of those suspected of criminal activity. I have seen it in farmers repeatedly exposed to pesticides and herbicides, in hospital and industrial workers and in military personnel in contact with toxic chemicals, specifically toxic gases.
    I will discuss these at a later date as Secondary M.E. They do have one thing in common, and that is they also have a diffuse CNS injury as noted on brain SPECT scans. The diagnosis is made by history, as the actual cases are very difficult to diagnose due to the inability to assess brain levels of toxins in a live patient.
    Often these Secondary M.E. diseases are more severe than the infectious M.E. cases.
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  5. voner

    voner Senior Member


    thank you for your extremely clear, informative, and well written article. I had read the Hornig paper and I have read numerous blogs about the paper, however I still had numerous areas covered in the paper that I could not understand and had questions about because of my inability to understand some of the complex data analysis they did, etc. Your article answered most of those questions like... study design questions...... did the authors take into account sex differences? Age differences? .....

    your article also sifted through a lot of the side cytokine data and presented it in a format I could easily understand. I can't thank you enough. I suspect your ability to effectively communicate with Dr. Horning also make this article so valuable.

    I guess one inference that could be drawn is that the "chronic fatigue initiative" funders must've decided not to fund the Lipkin/Hornig microbiome study?

    thanks again.
    oceiv and Simon like this.
  6. Simon


    Monmouth, UK
    Thanks so much, it doesn't come easily so it's great to hear the blogs do what I'm hoping they do (and I'm much helped by guidance from a very talented writer).

    As you can imagine, Mady Horning was immensely busy with the launch of the paper but still found time to talk to me at 9am her time last Sunday, about 6 hours after having done an interview with a UK radio station... She's been immensely helpful.

    I think Ian Lipkin has already said publicly that the Hutchins Family Foundation have decided not to put further money into mecfs research (though they've alread put in a lot more than any other private donor). However, they have already funded a smaller and more limited microbiome study with Drs Lipkin & Hornig, which is underway. In a Reddit reply yesterday Mady said they were applying for funding from elsewhere to expand this study.
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  7. halcyon

    halcyon Senior Member

    Enteroviruses can do this. They can cause persistent infections lasting years.
    JaimeS and oceiv like this.
  8. Dr.Patient

    Dr.Patient There is no kinship like the one we share!

    Great study! We need to show a biological basis for our illness, even if not specific to our illness. It validates it's not all in our heads theory. Most important, however, that these cytokines patterns should definitely be different from the ones in depression, lest they all be attributed to depression.
    MeSci, aimossy and oceiv like this.
  9. snowathlete


    Thanks @Simon, really good article. As you point out, this was a meticulously designed study. I hope it sets the standard for other good researchers working in the field. Like you, I'm hopeful about this area of research proving fruitful with more study.
    MeSci, beaker, oceiv and 1 other person like this.
  10. Navid

    Navid Senior Member

    why did the hutchins family decide to no longer finance me/cfs research. i thought they had a family member who was ill with this disease? just curious

    RL_sparky, Blue, beaker and 2 others like this.
  11. Persimmon

    Persimmon Senior Member

    Thanks for another really helpful blog.

    A few questions:
    (1.) Do we have access to a study design protocol for this study, of the type submitted to or used in NIH funding applications?
    (ie a detailed description of what they intended to do, that was prepared prior to commencing the study)

    (2.) In the article, they speak of picking a 3-yr cut-off because of the characteristics of the data set and because of findings in studies of certain chronic infectious diseases.

    Do you know when they decided on this particular cut-off? Was it in the initial study design stage; after seeing the characteristics of their cohort; or after they had started analysing their samples?

    Did you learn whether they looked at any other duration cut-offs?

    As the data set was mainly of patients with duration <3yrs or >8yrs, is it fair to say that the same findings might have been obtained had they set their cut-off at 8yrs (or for that matter, at any point bw 3-8yrs)?

    (3.) Their cohort consisted of the combined NIH/XMRV and CFI cohorts. I think the former is restristed to acute-onset virus-like/virus cases; I'm unsure about the latter but suspect it isn't restricted in this way.

    Have you formed a view as to whether this study's findings are more strongly/only supported with respect to acute-onset viral cases?

    (4.) Cheney is well known to have proposed the idea that the disease has distinct stages. For well over a dacade, he's been arguing there are three stages to it.

    Do you know of any previous cross-sectional studies that have attempted to stratify their cohort into disease-progression stages?
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  12. Simon


    Monmouth, UK
    Nothing posted as far as I know. While pre-study registration is now the norm, or at least expected in clinical trials, the same isn't yet true of other trials though I believe things are moving in this direction.

    I know th study was set up so they could study short duration patients as a subgroup; I don't know how the 3 year threshold in particular was set up.

    Because they set out to sample short (but not medium) duration patients they didn't have the data to understand what happens immediately post 3 years, though obviously they would love to know. And the lack of data 3-8 years precludes meaningful analysis of that time

    You're right about NIH cohort having a viral-like onset and no such restriction for CFI. Most of the short onset cases were from CFI so probably not a particularly 'viral' short cohort. But Mady Hornig said they will be doing more analysis to try to understand the impact of different types of onset esp viral v other.

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  13. free at last

    free at last Senior Member

    Interesting. I have never figured all this out. Though this paper seems to suggest much that seems to fit.
    Even as far back as 1995 Professor Leslie Findley (neurologist) at Harold wood hospital
    muttered Cytokines to he/s colleague, When I described what was happening to me. Clever man.
    Looking forward to seeing the other study when its released.
    oceiv likes this.
  14. Tally

    Tally Senior Member

    It might be because even in Younger's study Leptin levels were normal, but just seemed to follow the ups and downs of our energy level
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  15. 5150

    5150 Senior Member

    It could be anything: I was in the prime of my life and my health, when struck down by a sudden onset"bad flu about a week-long". I have never recovered or into remission or those good things. Among the group of men I hung out with was someone who had recently returned from living at Lake Tahoe for 6months. He didn't appear to be sick, looked strong in good health. as men will do, we lifted some tankards together and that person was a regular at the house. fairly close quarters. some way, I feel he brought the causal agent for my ME with him. I am hetero... there was no hanky-panky going on with any of us. So i'd say it was the "Close quarters" where pathogens are easily spread that it got me.

    Now you tell me, does that say this particular sub-group is Contagious? It 's the real nasty version. btw, I am not in touch with that group anymore, so seeing "how others are doing" isn't possible. which is a shame; that would be valuable info. If this is a true story, doesn't it conclude that at least "a subset" can be Contagious?
  16. Aidan Walsh

    Aidan Walsh

    'internal ionisation radiation injuries' boken cromosones/translocations...'low level' radiation sickness which explains why no-one has ever been able to identify one single infectious pathogen

    to date including viruses, fungus, bacteria etc 'all' 100% 15 cohorts patients are Positives to radiation isotopes some now are on the Memorial list as a result of the decades of negelct...We have had 3 Mile Island, Chernobyl plus over 2,000+ Nuclear testings not counting now the

    spread of Japan at our doorsteps now...Talk about a massive kill off of people to come this sickness will now only grow a good friend of mine who also works in the Water filtration industry already said this to me 'the entire water table below Philadelphia is contaminated with radiation

    &amp; they do not know what to do about it now except continued chemical treatment processes...If any of you think this in 'not' radiation sickness you seriously need to give your heads a full shake...Think I'm kidding wait until all you kids get sick &amp; they get 'labels' in diagnosis after

    'labels' Blesses you have all been warned I told you so...May be a great idea to look into patterns of Cytokines of Chernobyl victims afterall Russian honest Scientists call CFS Radiation Sickness 'Disease' afterall they already have proof it 'is' radiation sickness the 21st Century cover-up...It's

    'not' HHV6-A or XMRV pure b.s. it's Radiation Sickness 100% even the 'epitope' found at University of Hawaii new that the 'epitope' found was not Ciguatera but something more with

    radiation in the fish...California is now infested with the highest levels of radiation &amp; theincidence of CFS will get much much higher now it will attack thyroids brains etc etc...
  17. Misfit Toy

    Misfit Toy Senior Member

    I love that Sasha! That's how I feel...I got it even with this crazy brain fog!
    Simon, oceiv and Sasha like this.

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