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Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2021, Lutz et al

Discussion in 'BioMedical ME/CFS Research' started by MSEsperanza, Sep 14, 2021.

  1. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    Lutz L, Rohrhofer J, Zehetmayer S, Stingl M, Untersmayr E. Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomolecules. 2021; 11(9):1359. https://doi.org/10.3390/biom11091359

    free full text: https://www.mdpi.com/2218-273X/11/9/1359/htm

    Abstract
    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multi-systemic disease characterized by debilitating fatigue that is not relieved by rest. The causes of the disease are still largely unexplained, and no causative treatment is currently available. Changes in the immune response are considered as fundamental in the development of ME/CFS. Thus, we aimed to evaluate the immunological profile of ME/CFS patients in a retrospective data analysis.

    As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed. Out of 262 ME/CFS patients, 64.9% had a reduction or deficiency in at least one of the listed immune parameters. In contrast, 26.3% showed signs of immune activation or inflammation. A total of 17.6% of the ME/CFS patients had an unclassified antibody deficiency, with IgG3 and IgG4 subclass deficiencies as the most common phenotypes. Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%.

    In summary, the present results confirmed the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant disease biomarkers, which might lead to targeted therapeutic approaches in the future.
     
    Last edited by a moderator: Sep 14, 2021
  2. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    The study had no control group but the values for each parameter were compared to norm values used for laboratory diagnosis.
     
    Last edited: Sep 14, 2021
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  3. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    I deliberately have not looked at the article itself because I want the possibilities of a diagnostic test and a treatment to last a little longer in my imagination, before it goes back to just being a potentially interesting result that requires a lot more research.
     
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  4. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    Indeed.
     
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  5. Hutan

    Hutan Moderator Staff Member

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    Regarding the mannose-binding lectin levels:

    It is not clear from that the paper or the supplementary tables if the 32.1% of the ME/CFS patients had MBL levels less than 50 ng/ml. The normal range given in paper's supplementary table 1 is '<300 ng/ml' - possibly it was meant to be >300 ng/ml. From what I can find, MBL levels are typically over 1000 ng/ml in healthy people (1 ng/ml = 1ug/L)
    Frustratingly, the paper doesn't present the actual results in a way that allows us to see what they actually found. I'd love to see a scattergram of the actual MBL levels.

    I do think it's interesting.


    Some background on MBL:
    https://medlineplus.gov/genetics/condition/mannose-binding-lectin-deficiency/#inheritance
    So, if the 32.1% frequency in this Austrian study is correct, it's possible that the MBL deficiency is substantially more common in people diagnosed with ME/CFS.

    https://onlinelibrary.wiley.com/doi/full/10.1111/j.0300-9475.2004.01392.x
    https://pubmed.ncbi.nlm.nih.gov/11256742/
     
    Last edited: Sep 15, 2021
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  6. Hutan

    Hutan Moderator Staff Member

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  7. Ravn

    Ravn Senior Member (Voting Rights)

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    As others have said the data reporting is too sketchy to know quite what to make of the findings. Many of their patients had something out of range in their test results but it was different things for different people, apart from just one larger group with low MBL (which is large enough to be interesting). Hard to interpret. Were those with frank immune deficiencies simply misdiagnosed? Can all the different types and severities of immune deficiencies lead to a common pathway to ME? Can having ME lead to developing all sorts of immune deficiencies in some and to immune activation in others?

    Surprisingly they didn't compare short- and long-term illness duration. At least one other study has found differences in immune markers (different ones from the ones investigated in the present study I think), i.e. activation in short duration and exhaustion in long duration illness, and the present study had a large subgroup with "immune deficiency" and a smaller subgroup with "immune activation" so that would have been interesting to look at.

    In that context, it would also have been interesting to have had a more thorough investigation into how the subgroups matched phenotypes. Does the "immune deficient" subgroup match the phenotype that catches every infection going and, conversely, does the "immune activated" subgroup match the never-catch-anything group?

    In the same vein - though they probably didn't have the necessary data to do this in the present study - would their subgroups match the react-badly-to or get-a-boost from vaccination groups?
     
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  8. Hutan

    Hutan Moderator Staff Member

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  9. Hutan

    Hutan Moderator Staff Member

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    Yes, there's so many questions.

    It even seems possible that low levels of MBL might be a protective response to intra-cellular parasites
    The ambiguous role of mannose-binding lectin (MBL) in human immunity
     
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  10. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Interesting that you found that. Going through the thread I was just about to remark that MBL is generally thought of as protector against extracellular toxin producing bacteria like staph aureus and if anything might be a bad thing when it comes to intracellular pathogens.

    If pathogens have anything to do with ME then it is almost certainly intracellular pathogens such as viruses.

    I still think there is a huge worry over cohort bias. And my overriding thought is that anyone seriously interested in the immunology of ME would not publish a retrospective study like this, unless it was done on a population-based cohort with matched controls gathered independently of the project objectives. Such a cohort exists at CureME. Sadly, with the CureME team out of DecodeME they may not be able to continue providing such resource.

    It is time the ME research community got its act together on these things.
     
  11. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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