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nk function possible biomarker for MS?

Discussion in 'Other Health News and Research' started by heapsreal, Jan 9, 2013.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    : These findings from a prospectively defined analysis of a large randomized trial confirm CD56bright NK cell counts as a DAC HYP efficacy biomarker and further support their immunomodulatory role in RRMS. http://www.neurology.org/cgi/content/meeting_abstract/78/1_MeetingAbstracts/S31.004

    RRMS is relapsing and remitting multiple sclerosis.
    This is the same biomarker PHANU have found in cfs/me.
    I dont quite understand this study, i think its saying those with a better nk bright cell numbers had fewer lesions. Daclizumab HYP Treatment is a monoclonal antibodies and this improves nk bright cells??
    Could this DAC HYP be a treatment to improve nk function in cfs/me??
    Trying to find more on this DAC HYP if someone can help me out?
    ALso someone with a better mind then me could make more sense of the study for the rest of us to understand would be great too?
     
    merylg and alex3619 like this.
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Found this,
    Daclizumab high-yield process (DAC HYP) is a subcutaneous formulation of daclizumab and an investigational therapy for the treatment of RRMS, the most common form of MS. DAC HYP is a humanized monoclonal antibody that binds to CD25, a receptor subunit that is expressed at high levels on T cells that are thought to become abnormally activated in autoimmune conditions, such as MS. Data from previous clinical trials showed that DAC HYP increases CD56bright NK cells, which target the activated immune cells that can play a key role in MS without causing general immune cell depletion.
    Will increasing nk bright cells help us??

    "Not only did the number of regulatory natural killer cells increase in patients treated with daclizumab," says Dr. Bielekova, "but that expansion correlated with the treatment outcome--the more these cells expanded, the better the MS patients did during the trial. And the longer the patients were on the therapy, the more regulatory natural killer cells they had and the better they responded to treatment."
    "The best news is that natural killer cells are actually very efficient immune cells that fight viruses or cancers," says Dr. Bielekova, "so it appears that daclizumab doesn't damage the immune system. It only shifts the emphasis of the immune reaction from T-cells to natural killer cells. However, larger studies need to be performed to evaluate the safety of long-term daclizumab therapy."

    http://www.msrc.co.uk/index.cfm/fuseaction/show/pageid/1502

    interesting stuff, i think something like this looks like a promising treatment for us as its treating our most common biomarker, nk bright cells found by PHANU
     
  3. Sea

    Sea Senior Member

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    Will read it properly later, but looks interesting Heaps
     
    heapsreal likes this.
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Marco from PR here posted some links to similar studies in may, dont know how i missed it but i will put the links up to those studies showing nk function improving with daclizumab.

    http://www.pnas.org/content/103/15/5941.short
    Administration of daclizumab, a humanized mAb directed against the IL-2Rα chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4+ T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4+ and CD8+ T cells and significant expansion of CD56bright natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56bright NK cells and contraction of CD4+ and CD8+ T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56bright NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.

    what is daclizumab http://en.wikipedia.org/wiki/Daclizumab

    cheers!!
     
  5. alex3619

    alex3619 Senior Member

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    This implies T cells are a major mediating factor, and that blocking their function via CD25 leads to better NK function. This does not prove this will work in ME, but it does show this is a very promising lead to follow.

    Going back for some time now I have been saying sIL2r is important. I have very high levels. sIL2r is CD25 when it is free in the blood stream. Go figure.
    http://en.wikipedia.org/wiki/CD25

    There is a mystery here though. CD25 is also a marker for Tregs or regulatory T cells that suppress inflammation. How is blocking CD25 working? Tregs are known to suppress NK cells.
    http://www.ebioscience.com/knowledge-center/cell-type/t-regulatory-cells.htm

    These cells are anti-autoimmune, and anti-allergy. Are they being suppressed? If so what might that mean in other respects? Will boosting NK bright cells be enough to make up for lost autoimmune and allergy resistance?

    Now CD25 is also expressed by gamma delta T cells. These are also anti-inflammatory, but have pro-inflammatory roles. Are they getting into lesions to heal and help, but because the trigger is never gone they persist in attracting a greater immune response and so greater inflammation? I hope to look into this at some point.

    One of the hypotheses I am looking at is "leaky" gut leads to gamma delta T cell migration, and they can then induce immune changes elsewhere in the body.
     
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  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I suppose its not directly increasing nk function but maybe a consequences of blocking IL2, but thats speculation?? Also blocking t cell function isnt really what we want or probably already have it as cd8 t cells function poorly in PHANU study.
    I think we need to pinch research from some of these immune/auto immune research studies and apply it to us ME.
    daclizumab when googling i did see a paper from a PHANU researcher(Dr Staines) mentioning this but it was in passing as he mentions more about his vasoactive peptide theory? So hopefully PHANU are looking into this.
     
  7. alex3619

    alex3619 Senior Member

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    Tregs are suppressor T cells. So are gamma delta T cells. Both express CD25. So suppressing them will boost not decrease T cell function I suspect - I have not researched this yet.
     
  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I mean we already have suppressed t cell function?
     
  9. alex3619

    alex3619 Senior Member

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    Yes I think we might have suppressed T function, but Tregs and gamma delta T cells can cause that. If you disable CD25 cells you might then enable cytotoxic cells to work better.
     

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