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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Suggest ME/CFS priority studies to Norwegian govt by 20 April & prepare to vote for them in PR poll

Discussion in 'General ME/CFS News' started by Sasha, Apr 13, 2016.

  1. Sasha

    Sasha Fine, thank you

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    Some of you may have seen this thread, started by @Kalliope, on the Norwegian Research Council's very exciting call to patients, carers, doctors and others to submit their ideas for research to help patients. The deadline is May 3 (just under three weeks away).

    I don't know whether a national research council has ever asked patients to submit ideas for research before - either way, this is a fantastic opportunity for all of us! @Mark is keen for Phoenix Rising members to contribute, and I've offered to organise it.

    You can help in two ways: (1) by putting forward the most important ideas that the Norwegians should be considering and (2) voting on the ideas so that we can tell the Council which ideas patients here think the most important.

    Of course, we're not all Norwegian but we're all patients, and any country's research agency should want to hear the best ideas. Interestingly, Norway seems to be using ME as the first disease that they're using this consultation process for, in recognition of the fact that they don't know enough about it.

    A focus of the call is on things that would have a short-term payoff but the call doesn't seem to be limited to that.

    The call talks about "diseases with prolonged fatigue" and although it clearly talks about ME/CFS, the definition being used might be quite broad so there are points that could be made about that. They say:

    If you have one or more ideas, please put each one into a single post with a subheading in bold (I'll give an example in the post below).

    Please do your best to answer each of these questions in no more than 180 words (1000 characters):
    1. In what area do we need new research into CFS / ME ? (Max. 1000 characters )
    2. What specific issues should be investigated further ? ( 1000 character limit )
    3. Why is this important for this population ? (Max. 1000 characters )
    4. Why is this important and useful for therapists ( health ) ? (Max. 1000 characters )
    If you struggle a bit with writing or finding references, we can crowdsource help on this (or other) threads.

    Please get your proposal into shape on this thread by 20 April and then I'll set up a poll to run 22 to 26 April. It would be great if there was lots of voting - large numbers will help to get the Research Council to take this seriously.

    Let's get cracking!
     
  2. Sasha

    Sasha Fine, thank you

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    Review of effects of routine testing and treatment of orthostatic intolerance in ME/CFS

    In what area do we need new research into CFS / ME ? (Max. 1000 characters )
    Orthostatic intolerance (OI) is known to be very prevalent and disabling in ME/CFS but patients who come to the clinic with their ME/CFS are rarely tested for it and so go untreated. Many patients are unaware of OI and don't recognise that they have it. A literature review to estimate prevalance should be conducted and published, and a large, random sample of ME/CFS patients should be tested for OI. Care should be taken not just to test for postural orthostatic tachycardia syndrome but also for neurally mediated hypotension, which requires a much longer tilt table test. The advice of clinicians such as Dr Peter Rowe and [**others, contact details] who have extensive experience of dealing with ME/CFS patients who also have OI should be sought. The effects of interventions on any patients found to be positive for OI should be summarised to guide future practice.

    What specific issues should be investigated further ? ( 1000 character limit )
    [**]

    Why is this important for this population ? (Max. 1000 characters )
    Orthostatic tolerance is a potentially treatable symptom that could improve the lives of patients a great deal if diagosed and then treated properly.

    Why is this important and useful for therapists ( health ) ? (Max. 1000 characters )
    This is potentially an important target for relieving symptoms.

    [This is an example of how to format a proposal - I didn't use the full word limit, and obviously I have some work to do!]
     
    Last edited: Apr 13, 2016
  3. Justin30

    Justin30 Senior Member

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    1. In what area do we need new research into CFS / ME ?

    • Defining of ME based on CCC/ICC patient Research
    • Research on Severe house and bedbound patients (massive amounts of tests including spinal taps)
    • Determine if this patient cohort has distict subgroups or stages like that in Cancer
    • This includes defining autoimmunity, Mitochrodrial Disease, Neurological, Immune or a mix

    What specific issues should be investigated further ?
    • Is ME really just Encephalitis with permanent damage and no reasonable treatment?
    • Is CFS the same as ME?
    • Neurological and Immune system abnormalities like in MS
    • Biomarker/biomarkers for CCC/ICC ME
    Why is this important for this population ?
    • The bottom line is Effective treatment
    Why is this important and useful for therapists ( health ) ?
    • they need a biomarker to test for
    • They need a list of diseases of exclusion....this means "rare disease" that have a direct overlapp in symptoms as true ME. (I understand the workup is big but so many are never given a full work up to exclude Autoimmune Diseases, Neurological Diseases, Encephalitis and Menengitis, Genetic Diseases, Mito Diseases)
      • A set of Drs needs to review symptoms and find diseases that directly overlapp with ME even if very rare
    • They need to able to recognize and treat immediately like as per what Dr Petterson said using IVIG and Antivirals at onset
    • All Drs need to be trained in Med School about this disease and we need a Center of Excellence
     
  4. Sasha

    Sasha Fine, thank you

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    @Justin30 - can you give your proposal an overall title that people can vote on at the end of the process, if you want your proposal to go through our voting process here? I think you've maybe got a lot of different proposals in that one proposal and you might want to split them out into separate. Also, I wasn't sure that your answers to Q4 related to the project(s) you were talking about in Q1.

    I think that, for the purposes of PR putting forward proposals, we can only deal with one proposal per post. (None of this is going to prevent people submitting their own proposals direct, if they want).

    Also (a general hint for everyone, me included!) we can't assume that the Research Council will know who these doctors are who we're referring to or will be familiar with their work - we'll have to give names, locations, and references to research papers. (I'll be editing my own post to put those details in).
     
    Last edited: Apr 14, 2016
  5. Sasha

    Sasha Fine, thank you

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    BTW, just to be clear - each person will be responsible for submitting their own proposal to the research council (I'll provide a translation of the form, and instructions) but PR will send along details of which proposals were most popular, and how many voted for them.

    And we can work together on this thread in trying to refine proposals up to the point where we're ready to vote, if people want. :)
     
  6. Justin30

    Justin30 Senior Member

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    :):)
    In what area do we need new research into CFS / ME ?

    • Research CCC/ICC Classification
    • Defining of ME based on CCC/ICC patient Researcarch on Severe house and bedbound patients (massive amounts of tests including spinal taps)Determine if this patient cohort has distict subgroups or stages like that in Cancer. This includes defining autoimmunity, Mitochrodrial Disease, Neurological, Immune or a mix
    What specific issues should be investigated further ?

    • Research into well defined cohort of CCC/ICC ME patients to look for a biomarker (ie. NK function, Lesions on Brain Stem, white mater spots, cytokines etc or is ME really just Encephalitis)

    Why is this important for this population ?

    • The bottom line is Effective treatment for now likely drug trials, drug repurposing, new drug development.

    Why is this important and useful for therapists?

    • They need a biomarker to test for on a well established group of patients CCC/ICC Defined. So they dont just give the CFS label out. So they can treat effectively. So they are trained correctly.

    I find it tough to summarize the biomarker issue as there are so many areas it impacts take what you like from it. Maybe someone else can add to it.

    I just think that symtoms and symptom clusters under the CCC/ICC Criteria need to be looked at further and in the mean time we need thorough medical work ups done from the onset of the illness ex:

    All tests listed in CCC/ICC Criteria to establish a baseline. This baseline is rarely established and paitients are left fighting for testing when it should be done from the get go. Examples are immune panels, cytokine panels, SPECT Scans, PET Scan, Microbiome testing, SIBO Test, Viral testing ( following what is done in the US with Viral Titers), Co Infections, OI Testing (thorough if symptoms overlapp with ME DX), etc.
     
    Last edited: Apr 14, 2016
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  7. Jenny TipsforME

    Jenny TipsforME Senior Member

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    I'm taking it that we're doing a sort of friendly peer review process here?
    Agree this is important issue, especially as people missing treatment. This Google scholar search seems to show it was a popular topic in the late 90s
    https://scholar.google.co.uk/scholar?q=incidence of Orthostatic Intolerance cfs&hl=en&as_sdt=0&as_vis=1&oi=scholart&sa=X&ved=0ahUKEwi7oonAqZXMAhVBExoKHR-ZDc8QgQMIGTAA
    Do these studies already show what you want to know (haven't read them myself)?
    Why did it go off the boil? More of a ME politics thing? Eg not wanting to give us tilt table in UK.

    Wondering if worth studying the decision making process/knowledge of gps for if they test for Orthostatic Intolerance, especially as initial tests can be free. For example, I've complained of dizziness since 2000 and even had expensive ENT tests and MRI in 2008 but took until I suggested POTS in 2014 for poor man's tilt table and standing blood pressure to be checked. Recent large UK POTS survey showed only 7% had been picked up by the gp.

    Also, seeing as we know most of us have OI, could the emphasis be more on treatment? Exercise is often pushed for POTS, is this the same for NMH? Is this just to be ignored for us or is it OK under anaerobic threshold? Are standard medications (beta blockers, midodrine, fludro) more/less effective if your OI related to ME?
     
    Last edited: Apr 17, 2016
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  8. Jenny TipsforME

    Jenny TipsforME Senior Member

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    I haven't settled on an idea yet but back on the other thread I've added an idea about pedigree case studies.

    I'm also interested in the thinking behind Jarred Younger's new Gulf War study design

    He's deliberately studying neuroprotective/anti inflammatory substances that won't need extensive approval to be used so that if any of them are beneficial patients can use straight away when results are released.

    Have to make a decision quick, or write up several ideas quickly!
     
    Last edited: Apr 17, 2016
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  9. Jenny TipsforME

    Jenny TipsforME Senior Member

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    Extended Family Extensive Medical History and Genome Analysis in Families with Multiple ME Patients

    1. In what area do we need new research into CFS / ME ? (Max. 1000 characters )
    There is already good evidence of a genetic predisposition to ME, with a hereditability estimate of around 50% (2nd World Conf does anyone have a better ref for this?). There is also evidence of mitochondria dysfunction, cardiovascular and autonomic impairments (which can have a hereditability element). It would be useful to do in-depth medical history and extended pedigree research on case study families where more than one person has had ME, taking a broad view of different health conditions. Depending on resources, this would include Genome Wide Association or a focus on areas of recent ME research advances such as mitochondrial DNA, immune function, MTHFR gene mutation and conditions related to dysautonomia such as Ehlers-Danos Syndrome. How do family members’ symptoms of other illnesses relate to recent genetic ME research? For example, hablogroup H has been associated with Post Exertional Malaise; J with joint pain and U with less bloating in ME (Billing-Ross et al 2016). Do family members with these hablogroups experience these symptoms in the absence of meeting ME diagnosis criteria?

    2) What specific issues should be investigated further ? ( 1000 character limit )
    It would be interesting to find out if genetic variations related to ME can be expressed as different conditions in other family members, or as variations which would not be severe enough for diagnosis. This idea is inspired by a paper posthumously analysing the medical history of Charles Darwin’s family (Hayman, 2013). Many of his relatives suffered chronic illness but in different forms (including the appearance of ME/CFS). This paper speculates a specific A3243G mtDNA mutation caused the different symptoms. What is more interesting for ME research is that “the detailed, lifetime history of his illness and those of family members shows us the range of symptoms that may occur with the one mtDNA abnormality”.

    Any research on participants with ME should also include careful recording of length of illness, apparent triggers, severity, the nature of symptoms and other co-morbidities for use as further comparison or subgrouping.

    3) Why is this important for this population ? (Max. 1000 characters )
    This could be an important element of identifying hereditary causal factors, which in turn could identify effective treatment. It may also be possible to identify differences in relation to triggers. In relatives who have similar mutations, but do not develop ME, what life experiences have been different for these individuals? In particular, what has their experience of infectious disease been? Does anything appear to be protective against ME, despite having a genetic predisposition? This could be useful for younger relatives who are at risk of ME.

    If the families do not demonstrate clean Mendelian segregation patterns, does this suggest the possibility of multiple underlying genes requiring further research?

    4) Why is this important and useful for therapists ( health ) ? (Max. 1000 characters )
    If family members have genetic mutations in common, but different expressions of illness, it may be that existing treatments for their other conditions are beneficial to ME patients with this specific variation. Information about patient reaction to drugs may also come out of this research (for example the families may be more often poor metabolizers). There may be useful preventative precautions for other family members, or treatment that could be taken early if relatives show initial symptoms.

    It could lead to useful subgrouping, as patients with different mutations are likely to need different treatment. For future patients, with the same mutation as those studied, it would not be necessary to analyse their extended family tree to get the relevant information.

    Possible References

    Hayman, J. (2013). Charles Darwin’s Mitochondria. Genetics, 194(1), 21–25. http://doi.org/10.1534/genetics.113.151241

    Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2016 Jan 20;14(1):19. doi: 10.1186/s12967-016-0771-6. Billing-Ross P1, Germain A2, Ye K3, Keinan A4, Gu Z5, Hanson MR6.

    Jason, L. A., Zinn, M. L., & Zinn, M. A. (2015). Myalgic Encephalomyelitis: Symptoms and Biomarkers. Current Neuropharmacology, 13(5), 701–734. http://doi.org/10.2174/1570159X13666150928105725

    Bhattacharjee, M., Rajeevan, M. S., & Sillanpää, M. J. (2015). Prediction of complex human diseases from pathway-focused candidate markers by joint estimation of marker effects: case of chronic fatigue syndrome. Human Genomics, 9(1), 8. http://doi.org/10.1186/s40246-015-0030-6

    International Consensus Primer (2012) http://www.me-ireland.com/ICC primer.pdf
     
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  10. Jenny TipsforME

    Jenny TipsforME Senior Member

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    I'd appreciate advice on a better reference for hereditability and if my genetics terminology is used correctly. I don't have any official background in this area but I'm learning for free from a Coursera course aimed at doctors: https://www.coursera.org/learn/personalizedmed/home/welcome

    I have some other ideas, so I might just churn some more out and see what chimes with people, energy permitting.
     
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  11. mango

    mango Senior Member

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    Have Fluge & Mella been mentioned yet?

    I'd like them to support Fluge & Mella's current and planned ME research (RituxME, CycloME and everything else they have going on), including sub studies and especially any new clues their research will turn up along the way.

    If they are looking for something quick, what could be better than building on what is already underway?
     
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  12. Jenny TipsforME

    Jenny TipsforME Senior Member

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    OK here is another one, a bit rushed:

    Glucose Metabolism Dysfunction and Personalised Nutrition in ME
    1. In what area do we need new research into CFS / ME ? (Max. 1000 characters )
    Anecdotally many people with ME complain of issues to do with sugar, but are not usually diabetic. Some people cut down portions of carbohydrates and others cut out refined sugar. One study found that a low sugar diet was not significantly different from a healthy eating control diet, contrary to patient perception (Hobday et al, 2008).

    However, in a recent study people with CFS were shown to have elevated glucose levels, there appeared to be an inhibition of glycolysis (Armstrong, 2015). Another recent study, found striking biochemical differences in skeletal muscle cultures, including a lack of increase in glucose uptake following 16 hours of stimulation (in contrast to control cultures) despite remaining responsive to insulin (Brown et al, 2015).

    Is there an unusual metabolic problem with glucose in ME? For example, greater fluctuation than normally seen, apart from in diabetics? Can this be managed with any efficiency at the diet level or is it a more fundamental metabolic problem?

    2) What specific issues should be investigated further ? ( 1000 character limit )

    A study similar in design to the Zeevi general population study in Israel that had nearly 1000 participants could be useful (Zeevi et al, 2015). That study had 2 phases. Firstly they constantly measured blood glucose levels via a glucometer placed under the skin and recorded sleep and activity using an activity wristband (eg a fitbit). Participants recorded further information in real time about their food, mood and exercise regimes on an app. Obviously a ME study would add in symptom scales into this too and detailed information on activity would be essential. They also took a stool sample for microbiome information.

    The Israeli team then created ‘good’ diets that prevented blood sugar spikes based on data from the 1st phase of the study (results were surprisingly individual). They found that not only did blood sugar respond as predicted but that the ‘good’ diet was associated with positive microbiome changes too. Can this diet information be applied in ME too and used as a 2nd phase?

    3) Why is this important for this population ? (Max. 1000 characters )

    Energy metabolism dysfunction is a likely problem in ME and deserves further investigation. The 1st phase of this research can contribute valuable data about glucose metabolism in ME. The 2nd phase may provide an evidence informed approach to managing diet. Even if diet changes are not substantial enough to correct potential problems at the level of ATP production, is it beneficial for patients to keep glucose levels more consistent? In the absence of substantial research, patients find it hard to interpret information about diet and information is shared at an anecdotal level.

    In the Zeevi study they found surprising levels of individual difference in blood sugar reaction to food. For example, some people have a healthy reaction if foods include fat whereas for others this makes no difference. People’s response to food was also linked to their gut bacteria composition. There was a benefit to individualising diet advice. Can this general population data be useful for people with ME?

    4) Why is this important and useful for therapists ( health ) ? (Max. 1000 characters )

    Further information about patients’ glucose metabolism would be useful for medics. At the moment glucose issues in ME are rarely acknowledged in primary care, once diabetes has been ruled out. It maybe, depending on results, that treatment for other conditions could be used once the nature of the problem is known. This approach is also very likely to steer nutritionists to improved dietary advice for patients.


    Possible references

    Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics. 2015 May 30. doi: 10.1007/s11306-015-0816-5. Armstrong CW, McGregor NR, Lewis DP, Butt HL, Gooley PR.

    A. E. Brown, D. E. Jones, M. Walker, and J. L. Newton, “Abnormalities of AMPK activation and glucose uptake in Chronic Fatigue Syndrome,” PLoS ONE, vol. 10, no. 4, Article ID e0122982, 2015. View at Publisher · View at Google Scholar

    Hobday, R. A., Thomas, S., O’Donovan, A., Murphy, M. and Pinching, A. J. (2008), Dietary intervention in chronic fatigue syndrome. Journal of Human Nutrition and Dietetics, 21: 141–149. doi: 10.1111/j.1365-277X.2008.00857.x

    Zeevi et al., 2015, Personalized Nutrition by Prediction of Glycemic Responses. Cell 163, 1079–1094, November 19, 2015
    http://dx.doi.org/10.1016/j.cell.2015.11.001
     
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  13. Jenny TipsforME

    Jenny TipsforME Senior Member

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    @mango what about this?

    How does immune TH2 dominance relate to B cells and hormonal changes in women with ME?
    1. In what area do we need new research into CFS / ME ? (Max. 1000 characters )
    Current Norwegian research into Rituximab is exciting for patients worldwide (Fluge et al 2011, 2015). We would appreciate further sister projects related to immune dysfunction.

    For example, Fluge and Mella mention other studies which indicate immune TH2 dominance (Broderick et al 2010, Skowera et al 2004). The action of Rituximab involves wiping out B cells. Part of the function of B cells is regulation of the function and activity of other immune cells, including T-regulatory cells, and NK cells. In turn T-regulatory cells balance the proportion of TH2. Could it be that the success of Rituximab is related to downstream regulation (or resetting) of TH2? Would this sequence of events account for the delayed response to Rituximab (B-lympocytes are the current explanation)? Or are altered TH2 levels simply a sign of B cell problems?

    It would be useful to study existing treatments which shift TH2 to Th1 to answer these questions.

    2. What specific issues should be investigated further ? ( 1000 character limit )

    Th2 shift is also related to sex hormone fluctuation in the luteal phase (Russell et al, 2016). This is interesting in an Autoimmune condition effecting mainly women. Cannon et al (1998) found a lack of healthy variation in neutrophil count after the luteal phase of the menstrual cycle in ME. Older women show decreased NK cell cytotoxic function (another immune response influenced by hormonal cycle and B cells). Could TH2 dominance be related to endocrine dysfunction in ME? Does this have anything to say to the observation that onset during adolescence is sometimes accompanied by relapse at 35 years, which can be the start of perimenopause (what is Swedish ref that @Jonathan Edwards mentioned?)? Research from Vollner-Conna et al (2006) indicates that menopausal status can be a segregating feature for sub-grouping participants with ME.

    A study could separate a sample of women with ME who have clear TH2 dominance from those don’t and compare in relation to other aspects of ME history as well as hormone fluctuations, menstrual status and response to TH2 to Th1 shifting medication or supplements.

    3. Why is this important for this population ? (Max. 1000 characters )

    Some patients report a symptom variation of brainfog disappearing just before a viral infection. This is attributed to TH2 dominance problems in online forums (the shift to TH1 is easing ME symptoms, although only to be replaced by a new virus). In response, some patients attempt to create this shift at other times by taking medication or supplements which are reported to rebalance TH2 dominance. These include inosine (a cheap supplement version of Imunovir), jiaogulan/gynostemma tea, reishi mushroom capsules, astragalus, raw honey and ginger. Some ME/CFS doctors prescribe Imunovir or Isoprinosine. Dr Cheney recommends a pulsing treatment of two months on, one month off. It would be helpful to know whether it is worth attempting the Th2 to TH1 shift and if these techniques are effective.

    Also it appears to patients that ME mainly effects menstruating women (though not exclusively) and is related to immune function. It would be reassuring to understand more how these aspects interact.

    4. Why is this important and useful for therapists ( health ) ? (Max. 1000 characters )

    If there is a relationship between the effectiveness of Rituximab and TH2 dominance, then there may be alternative treatments for some patients with reduced risk of harm. Findings could point to treatment with hormonal steroids or existing shifters of TH2 to Th1 (which are often freely and cheaply available as supplements). If a clear hormonal pattern emerges, it could be worth looking into existing, widely available approaches such as contraceptive pills and Hormone Replacement Therapy.


    Possible references

    Fluge Ø, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, et al. (2011) Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study. PLoS ONE 6(10): e26358. doi:10.1371/journal.pone.0026358

    Fluge Ø, Risa K, Lunde S, Alme K, Rekeland IG, et al. (2015)B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment.PLoS ONE 10(7):e0129898.doi: 10.1371/journal.pone.0129898

    Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, et al. (2010) A formal analysis of cytokine networks in chronic fatigue syndrome. Brain Behav Immun 24: 1209–1217.

    Skowera A, Cleare A, Blair D, Bevis L, Wessely SC, et al. (2004) High levels of type 2 cytokine-producing cells in chronic fatigue syndrome. Clin Exp Immunol 135: 294–302.

    Russell L, et al (2016) Illness progression in chronic fatigue syndrome: a shifting immune baseline. BMC Immunol. 2016 Mar 10;17(1):3. doi: 10.1186/s12865-016-0142-3.

    Faas M, Bouman A, Moes H, Heineman MJ, de Leij L, Schuiling G. The immune response during the luteal phase of the ovarian cycle: a Th2-type response? Fertil Steril. 2000;74(5):1008–13.

    Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, et al. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998;18(4):291–8.

    Vollmer-Conna U, Aslakson E, White PD. An empirical delineation of the heterogeneity of chronic unexplained fatigue in women. Pharmacogenomics. 2006;7(3):355–64.

    NB my knowledge in this area only extends to reading these articles. I also have acquired dyslexia through ME, and have developed a reading technique which is searching for the keywords I'm after. It is very possible that I miss important details! Feedback from people who've more thorough/professional knowledge is appreciated.
     
    Last edited: Apr 19, 2016
  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Dear Jenny,
    I think you are thinking of the Norwegian epidemiological study that showed two age peaks. There is a thread on it somewhere.

    I fear that I have to say though that Th1/Th2 balance is a myth. In all my years as an immunologist I never came across any reason to think there is such a thing in humans. It was a buzz word in the 1990s but was superseded by Th17 and then a realisation that T cells aren't very important. B cells are not TH2 - they are B cells, and autoimmunity probably has nothing to do with problems with T cells. Nobody has yet found anything wrong with the T cells except maybe in diabetes and I am doubtful even there.

    The evidence we have at the moment is about B cells - a response to depletion. I think we should focus on trying to confirm something wrong with B cells rather than going off a what has been a wild goose chase in other diseases.
     
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  15. Jenny TipsforME

    Jenny TipsforME Senior Member

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    @Jonathan Edwards
    There is evidence of raised th2 in ME though (mentioned in those references inc Fluge et Al 2011 and the 2016 Russell paper ie they're not shying away from it as an idea). Do you have an explanation for it? Am I right in reading that b cells regulate T regulators which in turn regulate th2? Is the controversial more around th1/th2 balance? If they don't do very much then that's a different type of issue. Perhaps th2 are just elevated as a sort of byproduct of B cell issues?
    I can tell you're not keen on this idea in general, but if I changed the wording about th1/th2 balance would some researchers be interested?
     
    Last edited: Apr 19, 2016
  16. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    People write about TH2 dominance in papers because it is the buzz and it gets papers accepted and grants funded.

    The whole thing is a myth. B cells do not regulate T regs - it is unclear they regulate anything. T regs are probably of no importance in autoimmunity either - that is another buzz word - this time from 2000. And B regs were invented in my department and are now a buzzword even though they probably do not exist. Immunobabble is a potent religion, just as psychobabble.

    The original link between TH2 and B cells was that TH2 cells make IL-4 and that helps B cells. But TNF is made by TH1 cells and that is essential for B cell cluster formation and survival and TH1 cells also make gamma interferon which is needed for antibody production. The whole thing started with a sort of Yin Yang idea from Marc Feldman in the 1980s that has never had any empirical basis. It just sounds good and allows you to draw nice diagrams.

    The problem is that all this is so oversimplified. It is a bit like saying petrol drives cars and cars drive people and people drive horses so petrol drive horses - that level of analysis. The reasons why B cells go wrong in each autoimmune disease must be completely different in each disease - because you do not generally get more than one autoimmune disease at a time. If it just due to 'imbalance' you would have a mush of mixture of diseases. Everybody was quite sure RA was a TH1 disease and then they were quite sure it was a Th17 disease and now we can see that it is a B cell loop disease - and that is why nobody ever found anything wrong with any T cells and half a dozen sorts of anti-T cell therapy had no effect.

    TH1/TH2 research is just turning the money handle for people who want to be important and have lots of grants on their CV I fear. Fluge and Mella are doing the right thing in focusing on where the evidence is.
     
  17. Jenny TipsforME

    Jenny TipsforME Senior Member

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    Bristol
    So it's not so much that researchers will think the submission silly, but actually that they're likely to want to do it and it won't get us anywhere useful? I fear I'm better able to spot psycho babble than immunobable (my degree is psychology).
     
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  18. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yes, if they thought they could get money they would be flooding in to submit grants of TH1/TH2 balance, except that to be up to date it might need to be B reg control of NK cells or something equally nonsensical. Come to think of it TH1/TH2 would seem a bit passé these days.
     
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  19. Mark

    Mark Former CEO

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    Another me/cfs researcher has said the same thing about th1/th2 to me quietly...it's a shame that some of these pervasive notions aren't challenged publicly more often...
     
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  20. mfairma

    mfairma Senior Member

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    I skimmed the above and didn't see this mentioned, but recognizing the politics of this disease, it would be nice to see more research focusing on validating the patient experience, particularly on elements that are crucial to that experience or particularly difficult for outsiders to understand. The two-day CPET gives us valuable confirmation of an essential element of our experience, as does tilt table and other related lines of research in the neurocognitive space. I wouldn't mind seeing more research showing that even things as basic as listening to loud and/or cacophonous music or being exposed to bright and/or flashing lights can trigger PEM in sicker patients. There is great potential value, I think, in studies that make it easier for people to accept this disease, even if that work has less long-term value than finding tests and treatments.
     
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