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"Antibodies to adrenergic and muscarinic receptors in ME/CFS" (August 29 blog post)

drob31

Senior Member
Messages
1,487
This is interesting, it makes me think the following:

Molecular mimicry because of a protein a bacteria produces causes the autoimmunity. Perhaps your leaky gut contains too many of this bacteria, which cause the "MM." So when you eat certain foods, almost any food, this type of bacteria feeds on it and multiples, which would be why you feel terrible almost any time you eat something...
 

RogerBlack

Senior Member
Messages
902
Food doesn't affect me at all that way.
As a technical point, I'll note that viruses and parasites seem to trigger CFS/ME/SEID/... as well as bacteria.
I would expect that pretty much anything which generates an antibody response has the potential in some cases to create antibodies with accidental autoimmunity.
 

Solstice

Senior Member
Messages
641
Food doesn't affect me at all that way.
As a technical point, I'll note that viruses and parasites seem to trigger CFS/ME/SEID/... as well as bacteria.
I would expect that pretty much anything which generates an antibody response has the potential in some cases to create antibodies with accidental autoimmunity.

Have you tried an elimination diet? I didn't think food affected me this much either, but since I'm on a diet from Christine Tobback I feel a big difference. Now when I stray from it and eat food that I shouldn't, I do feel toxic.
 

KME

Messages
91
Location
Ireland
Nice to see converging findings. And these particular antibodies make a lot of sense symptom-wise (for me, anyway).

I thought Loebel et al's study was interesting in this regard too. I'm pasting a bit of a previous post of mine here for energy conservation purposes! Fluge and Mella collaborated with German researchers in a study with Norwegian and German patients looking at more closely at antibodies. The Norwegian patients were in the rituximab trial so they were able to begin to piece together some antibodies that may be at play. Loebel et al say “We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and b adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy.” https://www.ncbi.nlm.nih.gov/pubmed/26399744 (free full access when you click through).


Loebel et al also make an interesting point that regular testing won’t pick up these antibodies:

“Our observation of a decrease of M and b receptor autoantibodies in patients responding to rituximab, in whom levels pre-treatment were within the normal range of control subjects, suggests that we may miss functionally pathogenic antibodies by just assessing quantitative levels by ELISA.”
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
It's an interesting hypothesis, but it is not proven that molecular mimicry is a specific cause of Guillain-Barré syndrome, nor even the form/subset Acute motor axonal neuropathy (AMAN) often associated with Campylobacter jejuni. AMAN has been associated with other pathogens such as Zika Virus and likely Diptheria and Tetanus too, suggesting that molecular mimicry is not the primary cause.
 

Gingergrrl

Senior Member
Messages
16,171
Antibodies to adrenergic and muscarinic receptors in ME/CFS
Paolo Maccalliniin agosto 29, 2017
1,396 Words

https://paolomaccallini.wordpress.c...adrenergic-and-muscarinic-receptors-in-mecfs/

Excellent blog @paolo and I am so glad that you are continuing to write and share it with us. I wish I had the ability to read all of your blogs that are in Italian!

I have the autoantibodies to the adrenergic and muscarinic receptors (as you know) and if these turn out to be the biomarker for ME/CFS than it will turn out that was my diagnosis afterall.

Right now, my doctor feels that these autoantibodies show that I have "Autoimmune POTS" and contribute to my muscle weakness (combined with some other autoantibodies that I have). I wish I understood it all better.
 

vision blue

Senior Member
Messages
1,877
@gingergirl. did you do one of the mayo panels or some other testing place? Do you have a thread where you say more about your autoimmune pots?
 

Gingergrrl

Senior Member
Messages
16,171
@gingergirl. did you do one of the mayo panels or some other testing place? Do you have a thread where you say more about your autoimmune pots?

I have a long thread on my experience with IVIG and Rituximab but the autoantibody info is scattered all over the place. You should be able to find it in a Google site search.

I did the Cell Trend Panel from Germany and some Mayo Panels (PAVAL paraneoplastic Panel, Myesthenic & MuSK panel, and I think one other that I can't remember off the top of my head.

Hope this helps!
 

pattismith

Senior Member
Messages
3,931
"Figure 2. An increase in reactivity of sera from ME/CFS patients to M1 cholinergic receptors was reported by Tanaka and colleagues in 2003 (left). Loebel and colleagues found an increase in reactivity to M3, M4 cholinergic receptors and beta 2 adrenergic receptors in 2016 (right)."

Interestingly, M1 and M3 are involved in REM sleep (the dreaming part of sleep.
I don't recall my dreams, but when I use my TENS on my upper neck, at the head root, I can recall my dreams.
TENS can reduce shaking of hands in Parkinson also, so I think my TENS may activate my M1/M3 receptors in my brainstem.


"In this regard, it is worth noting that autoantibodies to muscarinic receptors M2 and M3, and to beta adrenergic receptors (subtype 1 and 2) have been already reported in orthostatic hypotension (OH)"

This paper talks about heart auto-immunity and Sudden Cardiac Death:


"Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies affect myocardial electrophysiological properties and were reported to be the independent predictors of SCD in patients with different heart diseases. Autoimmune mechanism is proposed for cardiac-related adverse reactions following human papillomavirus (HPV) vaccination.
The pentapeptid sharing between HPV's antigens, adrenergic receptors and muscarinic acetylcholine receptors supports this assumption. "
 

Gingergrrl

Senior Member
Messages
16,171
This paper talks about heart auto-immunity and Sudden Cardiac Death:

"Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies affect myocardial electrophysiological properties and were reported to be the independent predictors of SCD in patients with different heart diseases. Autoimmune mechanism is proposed for cardiac-related adverse reactions following human papillomavirus (HPV) vaccination. The pentapeptid sharing between HPV's antigens, adrenergic receptors and muscarinic acetylcholine receptors supports this assumption. "

@pattismith Does this article mean that just having the "Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies" (which I have) increases your risk of sudden cardiac death or does it mean only in people who have also gotten the HPV vaccine (which I have never had). I just wanted to clarify before I panic LOL :nervous:
 

pattismith

Senior Member
Messages
3,931
@pattismith Does this article mean that just having the "Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies" (which I have) increases your risk of sudden cardiac death or does it mean only in people who have also gotten the HPV vaccine (which I have never had). I just wanted to clarify before I panic LOL :nervous:
They propose that sudden cardiac death event after HPV vaccine may be related to autoimmunity against β2-adrenergic and M2 muscarinic receptors that are present in the heart.
Nothing confirmed, it's just an hypothesis (the paper is 2019)
But the fact is that these antibodies have been found in some people after this vaccine (2017 article):

"An epidemiological study conducted in Denmark by Mølbak et al. found that vaccinated subjects with severe adverse reactions had more interaction with medical services prior to vaccination compared with vaccinated subjects without reactions [24]. Furthermore, autoantibodies to G protein-coupled receptors in the nervous system, such as β2-adrenergic and muscarinic-2 receptors have been isolated from two subjects in the US [25, 26] and in a large proportion of a sample of patients in Denmark (Mehlsen J, unpublished data).
A recent systematic review details the evidence to support a role of such autoantibodies in syndromes of orthostatic intolerance, including POTS [27]. Autoantibodies to these receptors have also been previously linked with CRPS [28] and CFS [29]. This pathophysiology could explain the pattern of symptomatology that has been consistently described in the multiple case series reported, as well as the variety of diagnostic labels used by reporting physicians. Taken together, these findings may indicate that vaccination has served as a trigger for manifestation of an underlying autoimmune disorder in genetically predisposed individuals. "
 

SlamDancin

Senior Member
Messages
521
Interesting my alpha adrenergic autoantibody were positive not beta although I did test positive for m2. Interesting that it’s only m2 they think involved. Of course from memory I know that m2 and alpha adrenergic are connected. This sounds like the immune system trying to compensate for some extreme stress on the autonomic systems.
 

SlamDancin

Senior Member
Messages
521
@pattismith That’s really interesting. I actually stumbled onto the m3/REM sleep connection myself and so I’ve been taking Mestinon, magnesium glycinate and some Alpha GPC and BCAAs (mainly isoleucine) to try and increase REM sleep. Still can’t remember my dreams but I smoke a lot of cannabis which kills my ability to remember dreams and takes at least a week break to being back able to. They are always extremely unpleasant when I do have them some I don’t really mind but I do want my precious REM. @pattismith You are a treasure to this forum. Keeping it alive and beating me to research all the time. ✊🏿
 

Gingergrrl

Senior Member
Messages
16,171
They propose that sudden cardiac death event after HPV vaccine may be related to autoimmunity against β2-adrenergic and M2 muscarinic receptors that are present in the heart.

Thanks, Patti, for confirming the sudden cardiac death hypothesis had to do in cases with the HPV vaccine (and not randomly)!

Also, what does “G coupled protein” mean? I keep seeing this in threads re: autoantibodies.

@pattismith You are a treasure to this forum. Keeping it alive and beating me to research all the time. ✊🏿

I agree and thank you, Patti, for finding and posting all of this research! I really appreciate it.
 

pattismith

Senior Member
Messages
3,931
@pattismith That’s really interesting. I actually stumbled onto the m3/REM sleep connection myself and so I’ve been taking Mestinon, magnesium glycinate and some Alpha GPC and BCAAs (mainly isoleucine) to try and increase REM sleep. Still can’t remember my dreams but I smoke a lot of cannabis which kills my ability to remember dreams and takes at least a week break to being back able to. They are always extremely unpleasant when I do have them some I don’t really mind but I do want my precious REM. @pattismith You are a treasure to this forum. Keeping it alive and beating me to research all the time. ✊🏿
M1 and M3 are activated for REM sleep, see my thread about it here, where I found a way to have some dreams back (actually more nightmares, so not a perfect result so far).
I don't think ME/CFS is only one disease, but it seems we share common symptoms @SlamDancin
I just try to understand my own ME/CFS, and share my findings, in case someone may be concerned/interested as well.;)
 

pattismith

Senior Member
Messages
3,931
Interesting my alpha adrenergic autoantibody were positive not beta although I did test positive for m2. Interesting that it’s only m2 they think involved. Of course from memory I know that m2 and alpha adrenergic are connected. This sounds like the immune system trying to compensate for some extreme stress on the autonomic systems.

this a new research article on Narcolepsy, it's interesting as narcolepsy goes with short REM latency and vivid dreams.
Activating autoantibodies against G protein-coupled receptors in narcolepsy type 1 - ScienceDirect 2021

We tested the serum of ten narcolepsy type 1 patients (five female) for activating β2 adrenergic receptor autoantibodies, M2 muscarinic receptor autoantibodies, and nociception receptor autoantibodies.

Results
Ten of ten patients were positive for muscarinic M2 receptor autoantibodies (P < 0.001),
9/10 were positive for autoantibodies against nociception receptors (P < 0.001),
and 5/10 were positive for β2 adrenergic receptor autoantibodies (P < 0.001).

Conclusions

Narcolepsy type 1 patients harbored activating autoantibodies against M2 muscarinic receptors, nociception receptors, and β2 adrenergic receptors.

M2 receptor autoantibodies may be related to the occurrence of cataplexy and, moreover, hallucinations in narcolepsy since they are found in the same brain areas that are involved with these symptoms.

The occurrence of nociception receptor autoantibodies strengthens the association between narcolepsy type 1 and pain.

The connection between narcolepsy type 1, autonomic complaints, and the presumed cardiovascular morbidity might be associated with the occurrence of β2 adrenergic receptor autoantibodies.

On the other hand, the presence of the autoantibodies may be secondary to the destruction of the hypocretin pathways.
 

Martin aka paused||M.E.

Senior Member
Messages
2,291
this a new research article on Narcolepsy, it's interesting as narcolepsy goes with short REM latency and vivid dreams.
Activating autoantibodies against G protein-coupled receptors in narcolepsy type 1 - ScienceDirect 2021


For me it shows what I've already thought: that these AAB can't be specific (in terms of exclusively positive) for ME. Otherwise more than 30% would have been tested positive.
Interestingly they don't test for the AAB at Charité themselves. I had the possibility to look at a doctor's letter signed by Professor Scheibenbogen. They tested a bunch of stuff in my buddy's blood, but not the AAB. Perhaps bc they have to calculate the costs and it wouldn't offer any treatment options.