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Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome

Discussion in 'Latest ME/CFS Research' started by Bob, May 30, 2011.

  1. Bob

    Bob

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  2. Snow Leopard

    Snow Leopard Senior Member

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  3. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    yes, im in this study, im hoping they continue studying cfs, we were hoping they would test us for xmrv but they seem gesitant to do this for some reason, maybe because its going off the track of what their trying to do.

    cheers!!!
  4. Megan

    Megan Senior Member

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    Thanks for posting bob and heapsreal for your ongoing information about this.
  5. oceanblue

    oceanblue Senior Member

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    Nice to have PR back online.

    Papers on immune functioning are not easy to understand largely because the immune system itself is so vast and complex. The terminology can be baffling (FoxP3 & VPACR2, anyone?) Anyway, I'm generally baffled, but I've tried to make some sense of this paper.

    Problem with the CFS cohort
    Unfortunately, the CFS sample, though large (n=95), is a bit flaky which compromises the results. They used the International/Ambiguities definition, which fine (basically just an updated Fukuda; Klimas and Jason are among the authors). But crucially Brenu et al failed to do a clinical evaluation as required. Instead they used a self-report questionnaire and patient records. Using these methods, 20% of the self-reported cases were deemed not to be CFS and it's likely quite a few more would have been excluded had they used a proper clinical evaluation. This failing inevitably casts some doubts over the findings.

    It's also worth noting that although Nancy Klimas is a co-author she merely critically reviewd the paper and was not involved in design, execution or analysis of the study itself.

    Key finding: further confirmation of Natural Killer Cell reduced Cytotoxicity
    For me the most important thing to come out of this paper was futher confirmation that the ability of Natural Killer cells to kill is reduced in CFS patients. The difference is large - NK cells kill 28% of target cells in controls but only 15% of target cells were killed in the CFS group (p<0.05) so it is very likely to be valid even allowing for the compromised selection of CFS patients. These figures are very similar to the Klimas findings last year (healthy controls 28% kill rate, CFS 12%, p<0.0005), but come from a different research group looking at different patients.

    More uncertainty in other immune findings
    As the authors say
    Apart from the NK findings above, this pattern of inconsistency continues.
    This study looked at some cytokines and found that both IFN-gamma and TNF-alpha were significantly increased in CFS patients. There have been inconsistent findings on this in the past and this is the largest study to have found increases, which is why it's such a shame they didn't nail down firm diagnoses for their CFS patients.

    They also looked in more detail at NK cell cytotoxicity. NK cells kill by injecting a cocktail of molecules into the victim cell, including Grazymes that chew up cell contents and Perforin that perforates the cell by forming pores in the membrane. Previous studies had shown reduced levels of these 2 molecules in CFS patients' NK cells, perhaps explaining why they were poor at killing. The Brenu study looked at gene expression of Granzyme and Perforin (rather than levels of the proteins themselves) and found that while Granzyme expression was decreased, Perforin levels were surprisingly increased. So, more confusion all round.

    New findings.
    The study also investigated several meausres of immune function that haven't previously been investigated in CFS patients and found various differences between patients and controls (eg FoxP3 and NK CD56bright expression) though whether or not these differences are significant or will be replicated by other researchers remains to be seen.
  6. oceanblue

    oceanblue Senior Member

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    Abstract

    Background
    Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterized by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients.

    Methods
    We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8+T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56bright and CD56dim) and regulatory T cells expressing FoxP3 transcription factor.

    Results
    Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-gamma, TNF-alpha, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in particular the CD56bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients.

    Conclusions
    Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

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