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Lombardi et al 2011 - cytokine signature in CFS

Discussion in 'XMRV Research and Replication Studies' started by jace, May 13, 2011.

  1. omerbasket

    omerbasket Senior Member

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    Have you been tested for XMRV? If so - have you been found to be positive or negative?
     
  2. oceanblue

    oceanblue Senior Member

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    I've found a recent paper on methodological issues in cytokine studies which suggests the sampling conditions in this study were far from ideal. It recommends that when taking blood for subsequent cytokine analysis, blood should be drawn into chilled tubes
    By contrast, this paper says blood was processed within 6 hours, which seems very slow - and makes no mention of ice and at room temperature cytokine degradation would be even faster.
     
  3. eric_s

    eric_s Senior Member

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    Could you check how it was done in other cytokine studies? Like the ones where Dr. Klimas participated, for example?
     
  4. acer2000

    acer2000 Senior Member

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    That might well be true and important, but the main finding of this paper was that patients with CFS symptoms and who also tested positive for XMRV had profoundly elevated IL-8. If the study you cite suggests that cytokines degrade if not processed immediately, wouldn't that suggest that the levels reported in that paper are actually too low instead of the other way around?

    Its probably more complicated than that... and might be different for each cytokine.
     
  5. oceanblue

    oceanblue Senior Member

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    It suggests to me that if you haven't treated your initial sample properly then everything else that follows is questionable - it's also possible that while the blood sample is sitting around for hours other processes are going on releasing cytokines into the blood which would no longer represent normal circulating cytokines levels. And unlike the Klmas study they didn't sample in the morning, another recommendation for consistent data. I don't understand why they didn't follow these basics.
     
  6. RedRuth

    RedRuth Senior Member

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    Did they only do CFS positive vs healthy? Surely this has nothing to do with XMRV unless they did a CFS positive XMRV negative control?
     
  7. jace

    jace Off the fence

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    Why does that make a difference? They were not trying to tease out subsets, but rather looking at the difference between XMRV+ ME patients and healthy controls.

    I came across this
    Now ME is thought to be (in part) a disregulation of the immune system, and Encephalomyelitis means an inflammation of the brain and spinal chord. In Lombardi et al, the cytokines that they found to be specifically uprated were

    I have bolded the ones that are mentioned in the macrophage study. Quite a clear correlation. Ginger tea, anyone?
     
  8. alex3619

    alex3619 Senior Member

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    A warning on ginger

    Hi, be very very wary of ginger. I tried it many years ago (1997?), and at very high doses all my ME or CFS fatigue disappeared. Entirely. Great, I found it! Not so.

    Every three days it started to lose effect. Every three days I had to double the dose. 100g per day became 200g, then 400g (yes, grams). At about the point that 400g was failing I realized that this was not going to work. Something was increasing the severity of the illness in response to ginger. I stopped taking it. Within a day or two I crashed, badly. I do not recommend the experience.

    On the removal of fatigue, there was some core of something that was not fatigue, something did not feel right - some kind of malaise that is hard to describe. It certainly was not a panacea. What it did do was for that short time it allowed me to expend effort to real exhaustion - real fatigue - something that I never experience with my illness because the post exertional relapse gets me before I can get that bad. I walked many miles for the first time in years, and was active all day long - until the crash.

    I have not written about this before because I knew some would try it. Be very very careful.

    Oh, and my friends were complaining they could smell me before they saw me - that much ginger gets noticed.

    Bye
    Alex
     
  9. RedRuth

    RedRuth Senior Member

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    Because it doesn't tell you anything about XMRV only about CFS sufferers. They can only say that the effect on cytokine levels is due to CFS not XMRV, unless they do the proper controls. The possible XMRV status of the patients is irrelevant unless they have a +CFS -XMRV group. It should really be called Chronic Fatigue Syndrome reveals a distinct inflammatory signature.
     
  10. lansbergen

    lansbergen Senior Member

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    I do not want inhibition of macrophages and T cells activation.

    I try to get them doing their jobs again.
     
  11. acer2000

    acer2000 Senior Member

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    Pos 3x by culture. Negative by antibody (although I think the tube was spun down wrong by the person who drew it before I shipped it).
     
  12. oceanblue

    oceanblue Senior Member

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    There are many ways of measuring cytokines (eg choose testing of plasma, serum, unstimulated PBMCs or stimulated PCMCs) and no one agrees what's best. The recent Brenu study even looked at cytokine mRNA/gene expression rather than protein leves. Closest comparison is with the Klimas study which like this one looked at plasma but processed blood within 2 hours - which is a lot better than the 8 hours that applies here but still substantially short of ideal. The Klimas study also had the advantages of only looking at women (cytokine levels vary by gender so you get a clearer picture by only looking at men, or women), and measuring cytokines in the morning (best time to do it). However, the Klimas sample was quite a lot smaller.

    Basically, there are no ideal studies. Until there are, it may be that the differences seen between studies are primarily down to methodology. Though it's worth noting that even for Rheumatoid Arthritis, an illness where there is a known role for cytokines (specifially TNF-alpha), they can't pin down a specific cytokine profile.

    So cytokines are hard to pin down anyway - and if the testing is sub-optimal then it's likely to be impossible.

    Another key factor is changes in the same individual over time (cytokine levels are so hard to pin down). Apparently Klimas & Fletcher are looking at repeated sample from the same individuals over time. Will be interesting to see this data in due course.
     

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