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Preprint Autoantibodies to Arginine-rich Sequences Mimicking Epstein-Barr Virus in Post-COVID and [ME/CFS], 2024, Sotzny et al

Discussion in 'ME/CFS research' started by Nightsong, Jan 1, 2025.

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  1. Nightsong

    Nightsong Senior Member (Voting Rights)

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    Abstract:
    Background: Epstein-Barr virus (EBV) infection is a known trigger and risk factor for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID syndrome (PCS). In previous studies, we found enhanced IgG reactivity to EBV EBNA4 and EBNA6 arginine-rich sequences in postinfectious ME/CFS (piME/CFS).

    Objective: This study aims to investigate IgG responses to arginine-rich (poly-R) EBNA4 and EBNA6 sequences and homologous human sequences in PCS and ME/CFS. Methods: The IgG responses against poly-R EBNA4 and EBNA6 and corresponding homologous human 15-mer peptides and respective full-length proteins were analyzed using a cytometric bead array (CBA) and a multiplex dot-blot assay. Sera of 45 PCS patients diagnosed according to WHO criteria, with 26 patients fulfilling the Canadian Consensus criteria for ME/CFS (pcME/CFS), 36 patients with non-COVID post-infectious ME/CFS (piME/CFS), and 34 healthy controls (HC) were investigated.

    Results: Autoantibodies to poly-R peptide sequences of the neuronal antigen SRRM3, the ion channel SLC24A3, TGF-β signaling regulator TSPLY2, angiogenic regulator TSPYL5, as well as to full-length α-adrenergic receptor (ADRA) proteins were more frequent in patients. Several autoantibodies were positively associated with key symptoms of autonomic dysfunction, fatigue, cognition, and pain.

    Conclusion: Collectively, we identified autoantibodies with new antigen specificities with a potential role in PCS and ME/CFS. Clinical Implication: These finding should prompt further studies on the function of these autoantibodies, their exploitation for diagnostic use, and of drugs targeting autoantibodies.

    Link | PDF (MedRxiv preprint, open access)
     
    Nightsong, Jan 1, 2025
    #1
    Yann04, Peter Trewhitt, Turtle and 5 others like this.
  2. Hutan

    Hutan Moderator Staff Member

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    Participants from the Charité Fatigue Centre, Berlin. The research team includes Carmen Scheibenbogen and Nuno Sepúlveda.

    The introduction was full of statements that I think are arguable. I keep wanting autoantibodies to be the cause of ME/CFS, but until now, I think the evidence has not matched the claims.

    Sampling design was okay, big enough cohorts for a preliminary study and good characterisation. All female, age matched. It isn't clear if there were differences in the storage time of some of the samples. Possibly the serum samples for the non-post-Covid samples came from a biobank?

    I can't comment on the analysis techniques. It looks as though variability not attributable to differences in the samples was high though.
     
    Hutan, Jan 1, 2025
    #2
    alktipping, Yann04, pooriepoor91 and 4 others like this.
  3. Hutan

    Hutan Moderator Staff Member

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    30,836
    Location:
    Aotearoa New Zealand
    Screen Shot 2025-01-01 at 7.49.13 pm.png
    Fig 2a
    individual serum IgG responses as Mean Fluorescence Intensity (MFI) corrected to the MFI of scrambled peptide

    I'm not seeing any differences there that are very exciting. There might be a difference for TSPYL5_133, for some of the patients.
     
    Last edited: Jan 1, 2025
    Hutan, Jan 1, 2025
    #3
    alktipping, SNT Gatchaman, Yann04 and 4 others like this.
  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Those differences cannot have any general pathological significance.
    It all looks very non-specific and very likely due to some confounding factor either in technique or population sample.
     
    Jonathan Edwards, Jan 1, 2025
    #4
    alktipping, SNT Gatchaman, Yann04 and 4 others like this.

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