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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Dysregulation of Protein Kinase Gene Expression in NK Cells from CFS/ME pts

Discussion in 'Latest ME/CFS Research' started by Kati, Aug 28, 2016.

  1. Kati

    Kati Patient in training

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    http://www.la-press.com/dysregulati...pression-in-nk-cells-from-chron-article-a5866

    Foreword from the authors:

    Dear Supporters,
    The National Centre for Neuroimmunology and Emerging Diseases (NCNED) would like to sincerely thank the Stafford Fox Medical Research Foundation, Change for ME Australia, The Alison Hunter Memorial Foundation, Mr Douglas Stutt and the Queensland Government for providing financial support for our latest publication.

    This current paper reports novel results of far reaching importance for CFS/ME diagnosis and possible pathology. The paper describes world first discoveries of kinase gene dysregulation associated with changes in calcium ion function. This research leads from previous significant papers we have recently published involving research into calcium ion channels in CFS/ME. Please refer to two of our recent publications reported in Biological Research and Clinical Application of Genetics.

    These publications reflect the commitment of our team in achieving the best possible outcomes for those with CFS/ME.

    Best Wishes
    Sonya, Don and the NCNED Team


    Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

    Anu Chacko, Donald R. Staines, Samantha C. Johnston and Sonya M. Marshall-Gradisnik

    Gene Regulation and Systems Biology 2016:10 85-93

    Original Research

    Published on 28 Aug 2016

    DOI: 10.4137/GRSB.S40036

    Abstract

    Background: The etiology and pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are unknown. However, natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in CFS/ME patients. Previous research has reported significant changes in intracellular mitogen-activated protein kinase pathways from isolated NK cells. The purpose of this present investigation was to examine whether protein kinase genes have a role in abnormal NK cell intracellular signaling in CFS/ME.

    Method: Messenger RNA (mRNA) expression of 528 protein kinase genes in isolated NK cells was analyzed (nCounter GX Human Kinase Kit v2 (XT); NanoString Technologies) from moderate (n = 11; age, 54.9 ± 10.3 years) and severe (n = 12; age, 47.5 ± 8.0 years) CFS/ME patients (classified by the 2011 International Consensus Criteria) and nonfatigued controls (n = 11; age, 50.0 ± 12.3 years).

    Results: The expression of 92 protein kinase genes was significantly different in the severe CFS/ME group compared with nonfatigued controls. Among these, 37 genes were significantly upregulated and 55 genes were significantly downregulated in severe CFS/ME patients compared with nonfatigued controls.

    Conclusions: In severe CFS/ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function. Similar changes in protein kinase genes may be present in other cells, potentially contributing to the pathomechanism of this illness.
     
    Last edited: Aug 28, 2016
  2. allyann

    allyann Senior Member

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    More promising research from NCNED. Full paper: PDF
     
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  3. Valentijn

    Valentijn Senior Member

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    Good patient selection, and the housebound and bedbound patients were classified as "severe", with the rest being "moderate":
    Other blood tests were done, basically the basic stuff done with diagnosis to exclude obvious stuff. ESR and CRP were higher for patients than controls, though not significantly so.

    The increase in mRNA amounts (gene expression) wasn't large ... all between 1.1 and 1.55 the normal amount. So 11-55% increases. The mRNA which had decreases were larger, going from 1.1 to nearly a factor of 2. They seem to be especially interested in calcium signaling, but it looks like only 6 of the statistically significant genes were related to calcium.
     
    Last edited: Aug 29, 2016
  4. msf

    msf Senior Member

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    Wow, they are finally using the ICC - hopefully Lipkin and others will follow suit.
     
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  5. hixxy

    hixxy Senior Member

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    I'm pretty sure they've been using both ICC and Fukuda when selecting subjects for a while, but just publishing under Fukuda. I agree it's nice to see them publishing with the ICC now.
     
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  6. msf

    msf Senior Member

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    That was a bit odd of them, if true. Why not say they fulfilled both criteria - surely no one could have found fault in that?
     
  7. Cheesus

    Cheesus Senior Member

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    I vaguely recall @Jonathan Edwards commenting a while back that he did not think NK Cell dysfunction was particularly well evidenced. Do you have any comments on this study, Jonathan?
     
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  8. msf

    msf Senior Member

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    As someone much less qualified than Prof Edwards, I will say that it doesn´t look very promising to me either.
     
  9. wastwater

    wastwater Senior Member

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    I was wondering about protein kinase C a while back
     
  10. Snow Leopard

    Snow Leopard Hibernating

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    After correcting for multiple comparisons, only 8 were upregulated, 27 were downregulated. Note that this for the severe group in comparison with the healthy controls - no such gene expression alterations were found in moderate cases.

    Also note, that the findings are specific to NK Cells, the results do not necessarily generalise to other gene expression studies using different cell types...
     
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  11. M Paine

    M Paine Senior Member

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    What an interesting paper. If anyone has any links to some decent diagrams for the pathways mentioned below, I'd really appreciate a link. I've come across a couple of them, but none that show the bulk of the protein kinases talked about.

    From the paper:

    "the protein kinase genes that are reported will be discussed in the context of intracellular pathways involved in JNK, STAT, and NF-kappa beta (NF-κβ) activity, and their role in Ca2+ regulation and NK cell lysis"


    Also, does anyone know what the term is for doing RNA'omic studies like this? And does anyone know if any researchers are doing the same for B-Cells?
     
  12. Snow Leopard

    Snow Leopard Hibernating

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    This is the one I usually remember:

    [​IMG]

    From Wikipedia: https://en.wikipedia.org/wiki/File:Signal_transduction_pathways.svg
     
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  13. M Paine

    M Paine Senior Member

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    Thank you. Was hoping to find something more like this, with information relating to each gene more in context with the paper. This one is good fo the JNK pathway, just looking for something similar for STAT/NF-KB:

    [​IMG]
     
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  14. M Paine

    M Paine Senior Member

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    I found the answer regarding RNA'omic's... Transcriptomics in the case of RNA only, or Expressomics in the case of RNA, Protein and other ligands.

    Also, Cornell are doing a B-cell, T-cell and NK-Cell Transcriptome study on CFS patients
     
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  15. Snow Leopard

    Snow Leopard Hibernating

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    I'm still looking.

    The MAP kinase kinase kinase's still amuse me though.

    Not sure how useful, but...

    Low res, but... JAK/STAT IL-6:
    https://media.cellsignal.com/www/images/proteomics/multi-pathway/jak-stat.jpg

    http://userscontent2.emaze.com/imag...023256300_JAK-STATpathwaysandinflammation.JPG

    JAK/STAT PDGF
    http://lsresearch.thomsonreuters.com/static/maps/635_map.png

    JAK/STAT various cytokines:
    http://saweb2.sabiosciences.com/images/JAK-STAT_Pathway_680.jpg

    https://www.qiagen.com/geneglobe/static/images/Pathways/JAK-STAT Pathway.jpg
     
    Last edited: Sep 5, 2016
  16. wastwater

    wastwater Senior Member

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    Wonder if FOXO genes are important
     
  17. AndyPR

    AndyPR Senior Member

  18. wastwater

    wastwater Senior Member

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