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Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome, 2003, Tanaka et al

Discussion in 'ME/CFS research' started by Hutan, Apr 29, 2023.

  1. Hutan

    Hutan Moderator Staff Member

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    An old study that has been included in a list of studies finding issues with G protein-coupled receptors.

    https://pubmed.ncbi.nlm.nih.gov/12851722/. Paywall

    Abstract
    The disturbance of the central nervous system and immunological abnormalities have been suggested in patients with chronic fatigue syndrome (CFS). We focused on immunological abnormalities against neurotransmitter receptors in CFS. Using a sensitive radioligand assay, we examined serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1), mu-opioid receptor (OPRM1), 5-hydroxytryptamine receptor 1A (HTR1A), and dopamine receptor D2 (DRD2) in patients with CFS (n=60) and results were compared with those in patients with autoimmune disease (n=33) and in healthy controls (n=30).

    The mean anti-CHRM1 antibody index was significantly higher in patients with CFS (p<0.0001) and autoimmune disease (p<0.05) than that in healthy controls, and positive reaction was found in 53.3% of patients with CFS. Anti-OPRM1 antibodies, anti-HTR1A antibodies, and anti-DRD2 antibodies were found in 15.2, 1.7, and 5.0% of patients with CFS, respectively. Anti-nuclear antibodies were found in 56.7% (34/60) of patients with CFS, but anti-nuclear antibody titers did not correlate with the activities of the above four autoantibodies.

    The patients with positive autoantibodies to CHRM1 had a significantly higher mean score (1.81) of 'feeling of muscle weakness' than negative patients (1.18) among CFS patients (p<0.01). Higher scores on 'painful node', 'forgetfulness', and 'difficulty thinking' were also found in CFS patients with anti-CHRM1 antibodies but did not reach statistical significance. In conclusion, autoantibodies to CHRM1 were detected in a large number of CFS patients and were related to CFS symptoms.

    Our findings suggested that subgroups of CFS are associated with autoimmune abnormalities of CHRM1.
     
    Last edited: Apr 29, 2023
  2. CRG

    CRG Senior Member (Voting Rights)

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  3. Hutan

    Hutan Moderator Staff Member

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    Thanks @CRG!
    Dotted line is the healthy control mean plus 2 standard deviations.

    Screen Shot 2023-04-30 at 7.50.46 am.png

    The chart indicates that there is a clear increase in the level of anti-CHRM1 antibodies in about half the CFS participants, but not in healthy controls. It looks pretty nice.

    "cpm" is counts per minute. Commercially available antibodies to human transmitter receptors were used as the positive standard.

    I'm not understanding how that index could produce a distribution of points for the healthy cohort that isn't centred around zero . If the denominator is constant, as it is, then shouldn't the healthy points on the chart be equally above and below the zero? Isn't that the point of the index, to assess antibody levels relative to the healthy cohort? The data points are pretty much distributed around zero for the three other antibodies assessed, but they aren't for the anti-CHRM1 one.

    I'd love for this to be a solid finding; can someone explain how that index calculation could produce the results for the healthy cohort shown in Figure 1A? I'm having one of those days when it is so hard to think.
     
    Last edited: Apr 29, 2023
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  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I forget the data on this but my memory is that Scheibenbogen looked at muscarinic receptor antibodies and did not find anything comparable.

    The lack of the normal centring around zero might reflect an artefact of pooling. A pooled serum is likely to have a higher value than average because antibody levels tend to vary to some extent logarithmically. All you may need is one high sample and the pool is highish.
     
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  5. Hutan

    Hutan Moderator Staff Member

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    I wondered about that, but Figure 1A plots the individual results for the healthy controls, and they look to be quite tightly clustered.
     
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  6. bobbler

    bobbler Senior Member (Voting Rights)

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    I'm no expert in this area so would only be a second pair of eyes trying to use common sense and maths, but the link to the full text doesn't open for me so I don't know whether that is the same for others who might have more answers. I don't know whether there are more clues re: the y-axis that might be pasted.
     
  7. bobbler

    bobbler Senior Member (Voting Rights)

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    googling (as couldn't open full text) found the following which I don't know whether is of interest or too much of a sidebar. https://www.meresearch.org.uk/research/ach-review/

    full paper about a page scroll down. it is from not long after this paper and is pulling together this with other 'of its time' findings. And in particular seems to be bringing in vasodilation side of things/the endothelial with the cholinergenic.

    And the following: https://www.sciencedirect.com/science/article/pii/S0889159115300209?via=ihub

    which is from 2016 and includes Fluge and Mella. And seems to note a significant but smaller proportion found of similar antibodies (though separated them 1-5). I like the writing (placing things in big picture) and it seems to bring a few ideas of the time together quite well, as well as a few interesting bells ringing as I guess research in this area goes around in jilted circles somewhat due to various reasons, and maybe some of these questions have gone answered and some theories fallen over - or not. but I was carking out half-way through so wouldn't feel confident citing anything just note it is worth a re-read.
     
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  8. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Yea the occasional [much] higher value would be interesting i.e. a potential autoimmune case --- treatable using rituximab ---
     
  9. CRG

    CRG Senior Member (Voting Rights)

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    SciHub is blocked by many service providers - there are a couple of ways around this. If you have a VPN try shifting the country the VPN points to as other than your own location - maybe necessary to choose the country where the SchHub link points to - in the above case that's Sweden (note .se). Alternatively use the TOR network. Some Scriptblockers might also work, though I don't know any specifically.
     
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  10. bobbler

    bobbler Senior Member (Voting Rights)

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    Thanks - will give it a try
     
  11. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I have not read the paper but the data seem to me to be presented in a my too predigested form. Antibodies that matter can be presented in a simple way that anyone can understand. As soon as people start creating peculiar indices I get sceptical.

    The human brain is quite good at seeing what means something in a simple plot of optical densities.
     
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