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Autoimmune Gene Expression Profiling of Fingerstick Whole Blood in Chronic Fatigue Syndrome, 2022, Wang et al

Discussion in 'ME/CFS research' started by LarsSG, Aug 23, 2022.

  1. LarsSG

    LarsSG Senior Member (Voting Rights)

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    Abstract

    Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.

    Methods In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.

    Results Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).

    Conclusions Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.

    Preprint

    Edit: The paper is now published. See post #5
     
    Last edited by a moderator: Oct 26, 2022
    merylg, janice, Starlight and 7 others like this.
  2. Denise

    Denise Senior Member (Voting Rights)

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    I am probably being oversensitive but I am irritated that the authors go back and forth between using ME/CFS and CFS.
     
  3. LarsSG

    LarsSG Senior Member (Voting Rights)

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    Interesting that this is from Bristol-Myers Squibb (the drug company).

    Patients self-identified as having CFS, though almost all said it was diagnosed by a doctor. Good to see about half of them were house- or bed-bound

    Viral testing was PCR of blood samples. 7 CFS with HHV6 out of 166, 1 control. 1 CFS with EBV. About half of the PCR cycle thresholds were very high (so very little viral DNA), the other half were pretty strong results.

    30% of the CFS patients reported an additional autoimmune disease diagnosis. I'm quite confused about what they were trying to do in their gene expression testing. Surely if you are looking for autoimmune related genes, you would want to remove those who you know have an autoimmune diagnoses from your analysis, but here they included them. It isn't clear to me if the differences they are finding between CFS and controls and between bedridden and non-bedridden CFS cohorts could be explained by the autoimmune disease alone or if it may be related to CFS.

    Looking just at the autoimmune group, they found higher levels of gene expression for a few genes in the bedridden versus non-bedridden group, but it seems like that could also just be due to more severe autoimmune disease.
     
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  4. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Haven't even glanced at the abstract etc. (above) but if Fluge and Mella found rituximab didn't work then how can B-cell/autoantibody immunity be relevant? OK vaguely recall that some autoantibody producing cells (plasma cells?) may not be killed by rituximab - so potentially a source of autoantibodies.
     
    Peter Trewhitt likes this.
  5. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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  6. Braganca

    Braganca Senior Member (Voting Rights)

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    Fluge and Mella still seem to be interested in rituximab maybe for a subset. That’s what I took from their recent video presentation anyway. One of their studies had greater effect using a larger dose for longer.

    I think this is really promising that Bristol Myers did this study and is showing interest! Great to see the use of remote via mail testing and online recruitment too.

    @Jonathan Edwards Did you have any thoughts on this study?
     
    Peter Trewhitt likes this.
  7. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    All I can say is that that sentence should not have got past any referee. What are 'autoimmune functions' supposed to be? I have not heard of these genes. They may well be involved in lymphocyte activation but that does not mean autoimmunity by ten miles.

    They are presumably looking at gene expression in circulating cells. That is pretty uninterpretable since circulating cells are by and large not doing anything interesting.
     
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  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    If 30% of patients also had autoimmunity that seems to make the whole thing nonsense. Surely you would want to exclude people with other autoimmunity.
     
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  9. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Apologies but my initial reaction is where's the proof - some autoantibody testing doesn't seem very reliable --- plus a positive doesn't necessarily mean you have an autoimmune disease.

    OK just glanced at the list of autoimmune diseases:
    "In addition, thirty percent (30%) of the ME/CFS patients have or have had autoimmune diseases (e.g. Hashimoto's thyroiditis, Fibromyalgia, IBD, POTS, Grave’s Disease, Crohn’s disease, Psoriasis, Rheumatoid arthritis and Sjogren's syndrome)."
    "e.g." is always worrying, "Fibromyalgia, IBD, POTS," - news to me, but then I don't know much.
     
  10. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I think the DecodeME genetic study might give a clue re a whether there's a subset with an autoimmune disease e.g. Fluge and Mella reported they found a higher incidence of HLA alleles(?) suggesting autoimmunity - think Chris Ponting checked the UK Biobank and didn't find the same genetic signal. So if DecodeME found an immune gene/HLA signature suggesting autoimmunity/immune dysregulation then that may support autoimmunity/immune dysregulation.

    I'm impressed by Fluge & Mella - great scientists - good to see them trying to help.
     
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