Antibodies to ß adrenergic and muscarinic cholinergic receptors in patients with CFS

kangaSue

Senior Member
Messages
1,400
Likes
1,996
Location
Brisbane, Australia
I think I have seen this link but will look at it again to be certain. It seems like not a lot is known about these antibodies and there is a lot of guess-work.
Au contraire, a lot is known about these antibodies in a research setting, just not a lot about to what extent they are a problem in the clinical setting.
 

Gingergrrl

Senior Member
Messages
14,593
Likes
43,573
Au contraire, a lot is known about these antibodies in a research setting, just not a lot about to what extent they are a problem in the clinical setting.
Does that mean unless you are actually tested and treated at Mayo Clinic, no one really knows what to do with the results in a clinical setting :bang-head:? I have no desire to go to Mayo, and am too ill to fly, and hoping that the doctor who tested me will give me some guidance of what to do.
 

kangaSue

Senior Member
Messages
1,400
Likes
1,996
Location
Brisbane, Australia
Does that mean unless you are actually tested and treated at Mayo Clinic, no one really knows what to do with the results in a clinical setting :bang-head:? I have no desire to go to Mayo, and am too ill to fly, and hoping that the doctor who tested me will give me some guidance of what to do.
I would think you only need Mayo to run the tests, you should be able to get treatment elsewhere. An Autonomic system specialist would be the best option for that because of the crossover of various body systems involved.
 

Gingergrrl

Senior Member
Messages
14,593
Likes
43,573
I would think you only need Mayo to run the tests, you should be able to get treatment elsewhere. An Autonomic system specialist would be the best option for that because of the crossover of various body systems involved.
This is what I am trying to do (an autonomic doc) and referred to pulmonary and hopefully soon to a neuromuscular doc, too. It is just a very slow process to make these things happen.
 
Messages
311
Likes
123
SO how do you fix the root of the problem? Taking immunosupressants is going to help in the short term but what about damage you more in the long term?

How do we stop the body from putting antibodies on things it shouldn't? Is it chronic infections and/or heavy metals which are dysregulating the immune system?
 

Kati

Patient in training
Messages
5,497
Likes
19,621
SO how do you fix the root of the problem? Taking immunosupressants is going to help in the short term but what about damage you more in the long term?

How do we stop the body from putting antibodies on things it shouldn't? Is it chronic infections and/or heavy metals which are dysregulating the immune system?
That's the million dollar question, isn't it?
Targeted therapy pharma will be happy to take it from the moment there is general consensus on cause and pathology/ physiology of illness.
 
Messages
311
Likes
123
That's the million dollar question, isn't it?
Targeted therapy pharma will be happy to take it from the moment there is general consensus on cause and pathology/ physiology of illness.
Chemotherapy followed with stem cells was an interesting treatment for MS. They say it was to ""reset"" the immune system.

But i guess if you had mercury lodged deep into your tissues, along with stealth pathogens causing your immune dysfuntion then you would relapse after this treatment if these things were still there?

Also this treatment is very risky and people with ME would not tolerate it.

I have heard tales of people removing amalgam fillings and having antibodies dissapear. There has to be a root cause for why the immune system is going haywire....
 

Gingergrrl

Senior Member
Messages
14,593
Likes
43,573
SO how do you fix the root of the problem? Taking immunosupressants is going to help in the short term but what about damage you more in the long term?

How do we stop the body from putting antibodies on things it shouldn't? Is it chronic infections and/or heavy metals which are dysregulating the immune system?
Am not sure if you are asking me but immunosuppressants are only one option and in my case, most likely will not be what I am given b/c the cancer risk is too high. Will most likely do IVIG or plasmapheresis to try to reduce or eliminate the auto-antibodies. We think in my case there were multiple triggers (too many to even list) and in a way the triggers do not even matter vs. getting rid of the auto-antibodies now. This will not apply to everyone.
 

Sushi

Moderation Resource Albuquerque
Messages
17,442
Likes
27,597
Location
Albuquerque
Chemotherapy followed with stem cells was an interesting treatment for MS. They say it was to ""reset"" the immune system.
I've posted here about my friend with MS who had this done--his MS stopped progressing for 5 years but is now once again progressing.
 

Gingergrrl

Senior Member
Messages
14,593
Likes
43,573
That is not how autoimmunity is perpetuated.
@Snow Leopard Stupid question but how is autoimmunity or auto-antibodies perpetuated? I have been trying to grasp this myself. I know the immune system shifts to the TH2 side (or whatever you want to call it) but what makes it stay there? What makes someone develop auto-antibodies (like the calcium channel antibodies, etc?) No worries if you don't know since many docs don't even know!
 
Messages
5,877
Likes
12,641
Location
South Australia
@Snow Leopard Stupid question but how is autoimmunity or auto-antibodies perpetuated? I have been trying to grasp this myself. I know the immune system shifts to the TH2 side (or whatever you want to call it) but what makes it stay there? What makes someone develop auto-antibodies (like the calcium channel antibodies, etc?) No worries if you don't know since many docs don't even know!
Jonathan Edwards has had a bit to say on this topic!

Summary of points:

Alteration in T-Cell phenotype or activation is not necessary for most autoimmune processes (all of the autoimmune conditions associated with autoantibodies). As an aside, I note that JE also doesn't think much of the benefit of dividing activated T-helper groups into 'Th1/Th2' groups)

Evidence to date about environmental factors perpetuating autoimmune disease is severely lacking - regardless of viral, dietary, poisons, mould, psychological stress etc. Despite such claims being regularly made by doctors.
(lacking beyond the trivial, eg Coeliac Disease requires Gluten exposure - but that doesn't exactly explain the illness)

Autoantibody syndromes persist due to the specific autoantibodies themselves interfering with the regulation and promoting the survival of those B-Cells (and/or plasma cells) that will end up producing those autoantibodies in the future. Specifically, it is not merely the presence of antibodies that attach to self-antigens that is important, but rather the presence of dysregulated antibody production due to feedback loops!

The specific shape of an antibody itself is due to stochastic factors. Which is to say it is due to chance.

It is not necessary for T-Cells to lose tolerance to self antigens for B-cell autoimmunity to persist. It is possible for a B-Cell receptor to be sensitive to a self-antigen, yet internalise both that self-antigen and a foreign antigen that may also be attached to it. If the B-Cell was to then present fragments of the foreign antigen on the MHC-II receptor, then it is possible for a T-Cell to activate that B-Cell, without any T-Cell receptors being sensitive to self-antigens. This has been clearly demonstrated in the case of Rheumatoid factors (that are basically antibodies that stick to other antibodies), I believe this evidence is mentioned in the JE paper below. If the B-Cell manages to survive to become an antibody producing plasma-cell, then a feedback loop could be induced. This process happens at a background level all the time (no one has zero autoantibodies), however most of the time these antibodies do not produce a sufficient feedback loop, hence no autoimmune illness is induced.

This process would primarily happen due to chance, although in my opinion it is possible that the initial trigger could be increased due to infection - but it needs specific things to happen, namely the self-antigen must readily form a complex with the foreign antigen, for the B-Cell to make the initial mistake. Once such a feedback loop has been induced however, it is no longer necessary for the infection or whatever to remain.

Apart from forum posts. you can read some of Jonathan's comments here:
https://www.researchgate.net/post/Are_there_studies_on_the_incidence_of_autoimmunity_in_spouses
And the 1999 article:
https://www.researchgate.net/public..._B_lymphocytes_drive_human_autoimmune_disease
 

Lolinda

weird OI: standing up stops my digestion
Messages
386
Likes
598
A basic question: how do these antibodies cause or contribute to the symptoms of CFS/ME? Prof Scheibenbogen, who published the paper which started this thread, is currently doing a treatment trial of removing the autoantibodies from the blood. So apparently she thinks they are causative in some patients. So there must be at least a hypothesis how this causation is brought about.
 

Lolinda

weird OI: standing up stops my digestion
Messages
386
Likes
598
They can attach to the adrenergic and muscarinic receptors, and possibly agonize or antagonize those receptors.
Certainly. Sorry, I made a mistake, I wrote "basic question", but I did not mean it that basic. :) What I meant was: CFS people have
- fatigue
- post exertional malaise
- brain fog
- some are wired but tired
- some cant sleep

so, how do we come from antagonizing these receptors to any of these symptoms?

What I mean I can illustrate by an example:
Here is my guess how it comes from antibodies to A1, A2, B1, B2, M1-5 receptors to POTS or to OH:
POTS:
These receptors are all in some way involved in blood flow regulation. When standing up, the body has to strongly regulate blood flow to prevent that blood pools in the legs. Blood vessels in legs need to constrict, blood vessels in the upper body need to dilate. When these receptors are blocked, then there is impaired blood flow regulation. The body will try to work against this with all force -> heart starts pumping like hell -> >30BPM heart rate increase upon standing up. (This is only a small part of the POTS issue, which is more an autonomic dysregulation, but maybe the essence of what concerns the antibodies.)

OH (ortostatic hypotension):
In addition to the above, receptor antibodies can be activating or dysfunctional. If activating (called also agonistic) receptor antibodies block a receptor responsible for vasodilatation, this simply means that the receptor constantly receives the command "Dilate!". Excessive vasodilatation means low blood pressure, dolbly so when standing up and all blood pools in the legs. This is what happens in OH:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275920/

Comments about my antibodies-->POTS and antibodies -->OH theories are more than welcome! Criticism and Addituons alike!
 
Last edited:

Gingergrrl

Senior Member
Messages
14,593
Likes
43,573
Do you have any more information about this? I'd be interested to learn more of her approach. I didn't know for example that removing auto-antibodies from the blood was possible. Sounds very interesting.
@MPaine, I absolutely have to re-read this entire 20 page thread to re-fresh my memory (including my own posts!) but I wanted to let you and everyone else know that I am in the process of arranging to have these tests run via Dr. Scheibenbogen's lab in Germany. I live in the US and contacted them via e-mail and they confirmed that I can send blood and have the testing done which I will then give to my doctor in the US. I do not yet have a test kit and am not sure exactly how it is done but will post more once I get this info.

I tested positive for the N-type calcium channel auto-antibody (via a test sent to the Mayo Clinic) and I have other autoimmune markers, positive ANA titer, and muscle weakness on breathing tests and EMG plus MCAS/allergic reactions. My case is extremely autoimmune even though it started out viral. It initially seemed to really match with ME/CFS but now we are not sure.

In any case, I had a very good response to one treatment of IVIG (with second IVIG in a few days) and I plan to do everything I can to knock down the auto-antibodies. Dr. Scheibenbogen's tests are not available in the US but if you contact the lab (Cell Trend) you can do them if you send the blood to their lab. Even if it is just academic at this point and does not change my treatment, I really want to know b/c I have had horrible reactions to meds that alter acetylcholine (both Benadryl and Mestinon) and I think this is why.

I am hoping the results will make it easier for certain treatments to be approved for me although no guarantee of this, especially since the tests would be considered "experimental" and not done by a US Lab. Feel free to ask me for more info (anyone!) and am hoping that removing the auto-antibodies will improve my symptoms with the ultimate goal of being able to walk without a wheelchair and breathe normally.

But one IVIG (literally one) has almost reversed my MCAS. I say almost b/c I continue to take ALL of my MCAS meds and supplements, and have not tried the foods that are the highest offenders, but short of that I am eating all regular foods again, eating any time of day without having to take a huge set of meds 30 min before eating, and no longer react to strong smells/odors. So the IVIG shifted something in my immune system away from the allergic and anaphylaxis type reactions. Whether this is temporary or permanent, I have no idea, but it blows my mind!

ETA: I wanted to clarify in case what I wrote was unclear, I am just arranging to have the blood tests run via her lab, any treatments that I do would be here in the US under the supervision of my own doctors, and I am not a part of her study and have never spoken with her in any context (although I wish I had the opportunity!)
 
Last edited:

M Paine

Senior Member
Messages
340
Likes
958
Location
Auckland, New Zealand
Thanks for responding. I had deleted my earlier message in case anyone wonders who/what post you were responding to this. This is because a few minutes after I posted that, I realised that probably the procedure she would likely look to use is plasmapheresis.

I'm sorry to hear that you are a severe case, good luck with the treatment. I hope you will update us on your progress. Looking towards addressing any auto-immunity seems like a promising treatment strategy.
 

Gingergrrl

Senior Member
Messages
14,593
Likes
43,573
Thanks for responding. I had deleted my earlier message in case anyone wonders who/what post you were responding to this. This is because a few minutes after I posted that, I realised that probably the procedure she would likely look to use is plasmapheresis.

I'm sorry to hear that you are a severe case, good luck with the treatment. I hope you will update us on your progress. Looking towards addressing any auto-immunity seems like a promising treatment strategy.
Oh, I had no idea that you had deleted the post that I quoted and you must have done it while I was typing! Am going to keep my post up in case the info is helpful to others.

She does use plasmapheresis in her study in Germany (which is rarely ever done in the US and none of my own doctors have ever done it) but it is not impossible. She also did IVIG in the study which is what I am doing now. My understanding is that PP done in Europe/Asia is a different procedure than what is done in the US and one removes only the antibodies vs. full plasma exchange or PLEX.

My understanding, from a complete non-science background, is that this treatment (the whole thing) can be helpful for those with autoimmunity and this is definitely the group or sub-group that I belong to. If I did not have proven auto-antibodies (plus maybe will have the exact ones that she tests for in the study, I do not know yet), then I would not pursue this treatment. But since I do, it felt like the right path to pursue and my doctors agreed.
 
Last edited: