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

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.

 

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



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.

 

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