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A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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Longitudinal investigation of natural killer cells and cytokines in CFS/ME

Discussion in 'Latest ME/CFS Research' started by Ember, May 9, 2012.

  1. SOC

    SOC Senior Member

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    Thanks, Alex. This immune stuff is still a giant puzzle -- or maybe 'complete mystery' is more accurate -- to me. I've got several bright/dim results (and none of the CD56CD16) on my immune test results, but without an expected range, I have no idea what to make of them.
     
  2. hixxy

    hixxy Woof woof

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    OF course not. That's precisely why this research is happening. How can they have reference ranges when they hadn't done the studies before?
     
  3. Marco

    Marco Old blackguard

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    Hi Alex

    This may be relevant :

    Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2R?-targeted therapy (daclizumab) in multiple sclerosis




    http://www.pnas.org/content/103/15/5941.short

    The described treatment response does imply that reduced CD56 Bright activity plays some role in MS pathology.
     
    heapsreal and Snow Leopard like this.
  4. hixxy

    hixxy Woof woof

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    Decline in circulating CD4+ and CD8+ T Cells is a good thing?? Both of these are already low for me at last check.

    Donald R Staines (email address removed)

    Government employee involved in the study. When's the government going to pipe up and provide some support for this illness?
     
  5. Snow Leopard

    Snow Leopard Senior Member

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    From: http://www.bond.edu.au/faculties-co...ion-health-and-neuroimmunology-unit/index.htm

    "Dr Don Staines, Public Health Physician at the Gold Coast Public Health Unit and joint manager of PHANU." (at Bond University)

    As far as the study goes, 28 years of repeated replications of reduced NK cytotoxic activity, at what point will others accept the data? The limitation is not of sensitivity, but of specificity (since it overlaps with other diseases), but if those diseases are ruled out? Secondly, we could combine these findings with other potential biomarkers for improved specificity.
     
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  6. Marco

    Marco Old blackguard

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    In addition to finding that reduced NK cytotoxity is stable over time, this, from the discussion, could explain a lot :


     
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  7. adreno

    adreno 3% neanderthal

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    You're not going to like this, but natural kill cell activity is also reduced in depression. I personally believe that depression is also an immune dysregulation syndrome, like ME. I believe there are many similarities, but also some differences. The upshot is, that if reduced NKCA is not specific to ME, then it is not usefull as a diagnostic biomarker, at least not on it's own.


    Psychoneuroendocrinology. 1989;14(4):295-301.
    Reduced natural killer cell activity in major depression: neuroendocrine implications.
    Nerozzi D, Santoni A, Bersani G, Magnani A, Bressan A, Pasini A, Antonozzi I, Frajese G.
    Source

    Department of Experimental Medicine, University of Rome, Italy.
    Abstract

    Natural killer cell activity (NKCA) was significantly reduced in a group of depressed patients, melancholic subtype, compared to sex- and age-matched controls. Corticotropin and cortisol values were significantly higher in the depressed subjects than in the controls, but no correlation between high hormone levels and low immunological activity was found in the patients.

    PMID:2554356
     
  8. adreno

    adreno 3% neanderthal

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    I know that SSRIs are not popular on this board, but in my opinion they are one of the safest and most effective group of medicines we have for ME at the moment. The following study shows that SSRIs help to normalize NKCA:

    http://www.ncbi.nlm.nih.gov/pubmed/2554356
     
  9. hixxy

    hixxy Woof woof

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    I's not an issue of popularity or not willing to give in to ME being a psychiatric disorder. Many of us plain cannot tolerate them. I'm guessing that our neurochemistry is so screwed up that there aren't any drugs out there that suit our particular kind of neuroendocrine dysfunction.

    ALL antidepressants make my overstimulation worse. Also, I have never recovered from mirtazapine (I know this is a TeCA), but I've tried all classes.
     
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  10. adreno

    adreno 3% neanderthal

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    I believe many who try antidepressants start at too high dosages. Certainly, if they follow their doctor's advice. I can only tolerate half a normal dose of fluoxetine.

    This might be another indication that MCAD is involved in many cases of ME, as the extra mast cell activation/degranulation causes excessive release of serotonin.
     
  11. ukxmrv

    ukxmrv Senior Member

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    I was "sold" antidepressants for their immune modulating and pain reducing properties but could not tolerate them due to the side effects. Was taking a SSRI when I had one of my later NK cell tests and it didn't appear to have any effects that I could see. Before my first NK cell test I had bloods taken to check serotonin levels and mine were fine. They were a few years apart and with different doctors.

    Maybe there is a different mechanism behind the NK cells problem in depression and those in ME? So many ME patients have taken SSRI's for so many different reasons that we would have heard if they were even a half decent treatment for ME.
     
  12. adreno

    adreno 3% neanderthal

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    Hum Psychopharmacol. 2006 Dec;21(8):503-9.

    An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome.

    Thomas MA, Smith AP.

    Centre for Occupational and Health Psychology, School of Psychology, Cardiff University, UK. thomasma@cf.ac.uk

    Abstract

    Two hundred and seventy-five patients fulfilling the Centre for Disease Control (CDC) criteria for Chronic Fatigue Syndrome (CFS) completed measures assessing illness history, global ratings of well being, sleep, activity and psychopathology at baseline, 6 months, 18 months and 3 year follow-up. Forty-nine of these patients had been prescribed antidepressant medication, namely Tricyclic drugs or Selective Serotonin Re-uptake Inhibitors (SSRI). Data from the current study suggests that patients in the antidepressant medication group recover at a faster rate over time when compared to the untreated patient sample. In addition, the positive effects of antidepressant therapy are maintained at the 3-year follow-up point. It appears from these data that the SSRI in particular are responsible for improvements in the condition. Most importantly, these improvements include a reduction in the levels of fatigue recorded by patients. These findings have not been demonstrated in previous studies of the effect of antidepressant therapy for patients with this illness and this may reflect the short time periods studied in the earlier research.

    PMID:16981220
     
  13. Jenny

    Jenny Senior Member

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    There are reference ranges, for CD56 I believe. Don't know about CD56CD16. I had some CD56 test results recently, with a control level indicated:

    NK phenotyping
    CD56dim 98.1% (control 92.4%)


    Please someone correct me if I'm wrong, but I've concluded that if I have 98.1% dim I must have only 1.9% bright, as the total refers to dim+bright.

    Jenny
     
  14. mobyjoby

    mobyjoby

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    I know very little about this but have seen a post on facebook saying that NK is decreased in depression BUT that the cytokine profile demonstrated has never been recorded in depression and looks more similar to that of MS. No idea how the person knows this but maybe others here have some insight into it. As I said I do not understand all this yet - being fairly new to it.
    they also mention it could look like an activated B cell profile.
     
  15. adreno

    adreno 3% neanderthal

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    Well, there is this study, showing difference of cytokine profiles, in ME/CFS and depression:


    Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):784-94. Epub 2010 Jul 4.

    An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

    Maes M.

    Maes Clinics @ TRIA, 998 Rimklongsamsen Road, Bangkok 10310, Thailand. dr.michaelmaes@hotmail.com

    Abstract

    There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2'-5' oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not 'comorbid' disorders, but should be regarded as 'co-associated disorders' that are clinical manifestations of shared pathways.

    PMID:20609377
     
  16. Snow Leopard

    Snow Leopard Senior Member

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    Unfortunately, not a proper randomised controlled trial. The double blind trials of SSRIs have not shown efficacy for depression or any CFS symptoms. MAOIs on the other hand have demonstrated efficacy for depression in CFS patients. Tricyclics too, but they have also been associated with notable side effects in CFS patients.
     
  17. adreno

    adreno 3% neanderthal

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    Right, you can choose to believe that the effects were all due to placebo, and that is of course possible. Nevertheless, an expert review have found antidepressants to be effective for treating somatic symptoms, including fatigue and pain. From the full text of http://www.ncbi.nlm.nih.gov/pubmed/19514866:

     
  18. FancyMyBlood

    FancyMyBlood Senior Member

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    Specific ME/CFS reviews found no effect of antidepressants on fatigue and other symptoms (although fluoxetine may be moderately effective for comorbid depression).

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907931/?tool=pubmed (Wessely alert)

    IMO antidepressants are not a valuable treatment for ME/CFS. Common sense would indicate that they could be effective for comorbid disorders, but even that evidence is very limited in ME/CFS. It's a little suprising given the broad criteria some trials used (e.g. Oxford definition).

    Given the recent research about similarities between interferon-alpha induced sickness symtoms and ME/CFS it's interesting to note that a recent study* showed that paroxetine was not able to positively impact anxiety, cognitive dysfunction, and neurovegetative symptoms after interferon-alpha/ribavirin treatment.

    *http://www.ncbi.nlm.nih.gov/pubmed/22353759
     
  19. adreno

    adreno 3% neanderthal

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    I find it ironic that you have to resort to a Wessely study to support your case. The study you quoted concluded that only CBT and GET are effective treatments for CFS, a conclusion that just about everyone on this board disagrees with. It is of course possible that the authors got it right about antidepressant treatment, but wrong about other modalities.

    The thing about SSRIs is that they have been shown to have properties that should be very advantageous in ME/CFS, including:

    - being neuroprotective/increasing neurogenesis
    - being anti-inflammatory
    - reducing autoimmunity
    - normalizing the HPA axis, at least partially
    - improving NKCA
    - decreasing pain

    They might not work for everyone, but considering some of the alternatives out there, the side effect and risk profile of SSRIs are quite benign, and IMO at least worth a try, especially if you have comorbid depression or anxiety.

    But in order to get back to thread topic, I would like to emphasize, that my point about depression (and antidepressants) in relation to NKCA is that reduced NKCA activity is a feature of depression also, that can be (at least partially treated) with antidepressants. What we really, really need at this point, is a diagnostic biomarker that is specific to ME/CFS, so that we don't get lumped with depression, or other disorders.

    EDIT: it might be that the reduced NKCA seen i ME/CFS is more pronounced than what is seen in other disorders, in which case it could still be a valuable biomarker.
     
  20. FancyMyBlood

    FancyMyBlood Senior Member

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    That's why I said 'Wessely alert':D

    I understand your argument about improving *possible* biomarkers in ME/CFS, but I believe it's a better idea to look at published research measuring relevant endpoints. A same argument can be made about those biomarkers in treatment-resistant depression. Assuming SSRI treatment has the same effect on those biomarkers in TRD compared to 'normal' MDD, it's still obvious those biomarker effects are not valuable for patients with TRD (at least not for their primary concern e.g. depression). The same can possibly be said if we look at ME/CFS and it's established antidepressant literature. Obviously, the literature is not conclusive (because of different definition criteria, the small amount of trials and differences in lengths of the trials), but I believe it's fair to say there is a lack of evidence to conclude antidepressants are effictive in ME/CFS.

    I wholeheartedly agree with you that SRRIs may be worth a shot. In contrast to some horror stories SSRI's are quite bengin indeed, although there are some reports that some PWME can't handle them.
     

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