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RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in CCD

Discussion in 'Latest ME/CFS Research' started by Kati, Jan 25, 2017.

  1. Kati

    Kati Patient in training

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    RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease

    Authors: Jerome Bouquet, Jennifer L. Gardy, Scott Brown, Jacob Pfeil, Ruth R. Miller, Muhammad Morshed, Antonio Avina-Zubieta, Kam Shojania, Mark McCabe, Shoshana Parker, Miguel Uyaguari, Scot Federman, Patrick Tang, Ted Steiner, Michael Otterstater, Rob Holt, Richard Moore, Charles Y. Chiu, David M. Patrick for the Complex Chronic Disease Study Group (Vancouver, BC, Canada)

    Clin Infect Dis (2017) ciw767.

    DOI:https://doi.org/10.1093/cid/ciw767
    Published: 18 January 2017
    Article history: Received: 25 August 2016 Accepted: 27 December 2016


    Abstract

    Background.
    Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients—individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis.

    Methods.
    Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections.

    Results.
    No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories.

    Conclusions.
    Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares.

     
    Last edited: Jan 25, 2017
    TiredSam, Valentijn, alex3619 and 4 others like this.
  2. Kati

    Kati Patient in training

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    I wonder if length of disease matters in this study. Seemingly it doesn't matter for Lupus patients as they are showing differentially expressed genes, but what about ME? What if they only picked patients who have been sick less than 3 years?
     
    alex3619 likes this.
  3. M Paine

    M Paine Senior Member

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    Auckland, New Zealand
    I heard mention that a group was looking at B-Cell/T-Cell RNA expression... look forward to a link to full paper if anyone has one.

    *Edit: Reading the methods again, it almost sounds like they did a blanket sequence of whole blood, rather than the individual cell lines.
     
    Last edited: Jan 25, 2017
  4. Tom Kindlon

    Tom Kindlon Senior Member

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  5. Butydoc

    Butydoc President

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    I believe Dr's Light from the University of Utah are looking at gene expression from lymphocytes and has found some profound differences with exercise. I'm not sure when they will publish their results. They did tell me that their patients who had OI showed a autoimmune gene expression. This is about as much info that I can provide presently. I'm involved as is my entire family with a gene expression study with this husband/wife researchers. My mother, brother, daughter and now son have developed ME/CFS. My other brother died from MS. They feel because of the unusual family history, they may find an abnormal gene expression that could lead to a pathway.
     
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  6. Murph

    Murph :)

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    Pleased to see they're alert to CFS being a disease of peaks and troughs.

    "... we cannot exclude the possibility that there are differences between CFS cases and controls confined to periods of symptom flares. We are presently investigating this hypothesis in a follow-up study involving RNA-seq data collected before and after flares induced by cardiopulmonary exercise stress testing."

    Would be interesting to see data by male/female and length of ilness too.
     
    alex3619 likes this.
  7. Kati

    Kati Patient in training

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    Your remark prompted me to look up the Big Data (OMF) study's list of tests. Here is a screen shot of the top of the list:

    IMG_1600.JPG

    I wonder if @Rose49 's husband can comment on whether the whole blood vs different cell line's RNA gene expression will provide additional information? (Only if he's not too busy)
     
  8. IreneF

    IreneF Senior Member

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    San Francisco
    Did this study include mitochondrial gene expression?
     
  9. Kati

    Kati Patient in training

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    Not too sure, @IreneF they publish bits by bits, the last paper was virus related (correction:mivrobial related) using the same cohort. They didn't find anything.
    https://www.ncbi.nlm.nih.gov/pubmed/27806082
     
    Last edited: Jan 26, 2017
  10. Valentijn

    Valentijn Senior Member

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    I'd like to see the actual numbers, but the paper won't load. My concern is that they have three control groups, which greatly dilutes the ability to attain statistical significance. The sample sizes are also quite small, which compounds the problem. And it sounds like a lot of comparisons are being made.

    This looks like a study which has been designed to fail.
     
  11. Kati

    Kati Patient in training

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    Weird the page won't load, it's loading for me, including all the supplements.
    https://academic.oup.com/cid/articl...eq-Analysis-of-Gene-Expression-Viral-Pathogen

    Try also through the journal website: Clinical Infectious Diseases.
     
    Valentijn likes this.

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