Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with CFS, 2016, Loebel et al

https://www.sciencedirect.com/science/article/pii/S0889159115300209?via=ihub
Open Access
Madlen Loebel 1, Patricia Grabowski 2, Harald Heidecke 3, Sandra Bauer 2, Leif G Hanitsch 2, Kirsten Wittke 2, Christian Meisel 4, Petra Reinke 5, Hans-Dieter Volk 6, Øystein Fluge 7, Olav Mella 8, Carmen Scheibenbogen 6


2016 paper but has been referred to a lot by other ME/CFS researchers

Abstract
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n=268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and β adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108).

Antibodies against β2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG1-3 subclasses, but not with IgG4. Further patients with high β2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated β2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder.

We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and β adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.

 

From the paper:

 

Here are the results from the paper:
Muscarinic autoantibodies



B adrenergic autoantibodies

 

Well, each dot is the level of the specific autoantibody for a person. So, yes, we can compare the mean, as shown by the red lines, which show little difference. And we can compare the range visually - and there is quite a lot of overlap. There are the p values, which suggest that there are differences, but they don't tell the whole story.

Knowing what we know about the unreliability of the Celltrend test, it does make the findings of the paper very questionable. I would be interested to know what the authors now say about this paper - maybe someone has said something?

 

Celltrend continues to offer these tests as diagnostic e.g.
https://www.celltrend.de/en/pots-cfs-me-sfn/important-publications/

Does anyone know if Professor Scheibenbogen or Charite Berlin benefits from the ongoing sale of these tests?


It's a bit interesting to look back on the Phoenix Rising threads discussing these findings. This is the main thread discussing the paper:
https://forums.phoenixrising.me/thr...ptors-in-patients-with-cfs.40109/#post-644031
At the time, there was excitement about rituximab as a possibly effective treatment, and so the parts of the paper that seemed to show a correlation between a reduction of antibody levels and response to rituximab probably helped with an initial burst of enthusiasm.

 

Yes, but that makes the ongoing sale of the test through Celltrend, particularly with the narrative that doesn't refer to the later work on the website, all the more strange.