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IgG stimulated β2 adrenergic receptor activation is attenuated in patients with ME/CFS, 2020, Hartwig et al

Discussion in 'ME/CFS research' started by Andy, Feb 9, 2020.

  1. Andy

    Andy Committee Member

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    Open access, https://www.sciencedirect.com/science/article/pii/S2666354620300120
     
    Simone, Joh, Marit @memhj and 11 others like this.
  2. Andy

    Andy Committee Member

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    Results are from only 5 subjects, CCC was used as selection criteria.
     
    Joh, Lisa108, ScottTriGuy and 4 others like this.
  3. lansbergen

    lansbergen Senior Member (Voting Rights)

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    16 IgG fractions were isolated from serum of 5 ME/CFS patients with elevated (CFS AABhigh) and 5 with normal levels (CFS AABnorm) of β2 AdR autoantibodies, and from 6 healthy controls (HC).
     
    Simone, ukxmrv, ScottTriGuy and 2 others like this.
  4. lansbergen

    lansbergen Senior Member (Voting Rights)

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  5. cassava7

    cassava7 Senior Member (Voting Rights)

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    With N = 5 patients, I can't see how this is anything but PR/advertisement for CellTrend. The study relies on CellTrend's assay for ME/CFS [1, 2]. Harald Heidecke is the CEO of CellTrend and Carmen Scheibenbogen is a co-author of the paper.

    In 2016, they published a similar study in the same journal: "Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome" [3].

    The results are interesting but not statistically significant. To my knowledge Charité Berlin is the biggest ME/CFS hub in Germany so it shouldn't be difficult to recruit patients like they did for the 2016 study (N = 268). Until then, these preliminary results are not telling much.

    [1] https://www.celltrend.de/en/pots-cfs-me-crps.html
    [2] https://me-pedia.org/wiki/CellTrend_diagnostic_test
    [3] https://www.sciencedirect.com/science/article/pii/S0889159115300209
     
    Last edited: Feb 9, 2020
    ukxmrv, Joh, lycaena and 5 others like this.
  6. Ravn

    Ravn Senior Member (Voting Rights)

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    Could this be a problem? Are they studying dysautonomia rather than ME? Do people with higher AABs have more dysautonomia? Would it have been better to have the AABs being the only difference between the 2 ME groups, rather than one group additionally having dysautonomia? Or is it a good way of trying to identify subgroups? So many questions...
    Dumbed down this seems to mean that IgG isolated from healthy blood does positive things to cells in vitro, but IgG isolated from high AAB patients fails do do those positive things. That seems to be something worth looking at in a larger cohort.
     
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  7. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    The results of this study are strange, and my first instinct was to blame the results on false positives on the Cell Trend test for CFSAABhigh, but then we find:

    Suggesting they are reactive, but in a different way. It is not explained in this study why some IgG become agonists and others antagonists.

    Also, β-arrestin recruitment inhibits the functioning of the GPCR and targets receptors for internalization. β-arrestin activity is basically a cellular response to aberrant kinetics of receptor activation.

    Interesting.

    This is not true, Kavelaars et al stated "Plasma noradrenaline levels in CFS patients did not differ from levels in healthy subjects (CFS, 1.47 ± 0.1 nmol/L, n = 14; control, 1.46 ± 0.2 nmol/L, n = 14; P = 0.98)."
    Wyller have several studies that find elevated basal catecholamines, however the participants of their studies were adolescents and there can be social factors (e.g. anxiety about the blood draw) leading to artefactual results.

    Suspiciously they didn't mention the other studies found that found normal catecholamines levels at rest.

    They also did not mention the several studies by Light and colleagues that found increased β2 Adrenergic receptor expression in leukocytes post-exercise challenge, despite normal or slightly low receptor expression before the exercise challenge.

    https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22210239/
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/
     
  8. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Haven’t read, but how can we determine if we have capillary endothelial dysfunction?
     
  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I have not looked in detail but it seem as if they previously found a (very slight) increase in antibody levels to receptors in ME/CFS patients but now they find that these antibodies do nothing to the receptors, whereas ordinary people's antibodies do do something. That seems pretty confusing.
     
    ukxmrv, cassava7, Sarah94 and 3 others like this.
  10. Sarah94

    Sarah94 Senior Member (Voting Rights)

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    Can anyone translate the abstract from Science into English?
     
    Lidia likes this.
  11. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    I'll give it a shot:

    We didn't find what we expected to find, but we found something else that was interesting. However we have no idea what it means. We suggest more research is required! ;)
     
    Robert 1973, Simon M, ukxmrv and 8 others like this.

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