Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME (2018) Scheibenbogen et al

[Luther Blissett]

I realize this is not an option in the UK (and I think you are assigned to a specific GP by where you live, although I might be incorrect on this).

Edit: I re-read my post and did NOT mean that there are not exceptional doctors in the UK vs. that you are assigned to a GP and don't have the freedom to get 2nd or 3rd opinions or travel to other doctors and pay privately, etc.

In Urban areas we usually get matched with a group of GP's. You can see any of them, it's usually more tricky to see a specific one in my experience. You're allowed to ask for a second opinion. There is always the option of private healthcare too, but most choose not to (and private healthcare does not provide emergency medicine).

The difference between our systems is that one is based on ability to pay, the other is supposed to be based on need. The problem we have is getting the 'need' recognised, that's why national guidelines are important. Broadly speaking

 

[adambeyoncelowe]

I know that access to testing is a major issue but even without testing, I haven't found many people on PR or S4ME that match my set of symptoms. I have definitely found many people with POTS and/or MCAS, but the muscle and breathing weakness that I had doesn't seem to match with many people here.



I am so sorry and a thyroid panel is pretty standard here for both PCP's and Endocrinologists. How do they test for Mono in the UK without serology?



I agree. It can be hard here, too, with the average doctor and it takes finding someone exceptional in my experience who is willing to dig deeper. I realize this is not an option in the UK (and I think you are assigned to a specific GP by where you live, although I might be incorrect on this).

Edit: I re-read my post and did NOT mean that there are not exceptional doctors in the UK vs. that you are assigned to a GP and don't have the freedom to get 2nd or 3rd opinions or travel to other doctors and pay privately, etc.

Most UK doctors don't test for things like EBV. They don't seem to want to give antivirals either. You're usually told to rest up and drink plenty of fluids, then sent on your way again.

 

[Gingergrrl]

In Urban areas we usually get matched with a group of GP's. You can see any of them, it's usually more tricky to see a specific one in my experience. You're allowed to ask for a second opinion. There is always the option of private healthcare too, but most choose not to (and private healthcare does not provide emergency medicine).

Thanks for explaining all of this, LB, and I really want to learn more about the different systems. In the US, if you have an HMO, then you are assigned to a PCP (GP) who is like the gatekeeper if you want to see a specialist. But if you have PPO, then you are not required to even have a PCP and can just go straight to the specialist (which is what I have). I think you guys refer to specialists as "consultants". And as you described, there are definitely more options in large urban areas vs. rural areas. But ironically sometimes there is a doctor who becomes very interested in a rare topic but is in a remote area (vs. a major hospital). It's all pretty random and fragmented over here.

The difference between our systems is that one is based on ability to pay, the other is supposed to be based on need. The problem we have is getting the 'need' recognised, that's why national guidelines are important. Broadly speaking

It is definitely based on ability to pay but the insurance companies will fight to the death to deny you care if you are not a good advocate, and know how to appeal denials, and stay on top of them. And many people are too sick to do this and the insurance companies count on this. I helped others with this as a social worker (before I got sick) so I am more knowledgeable how to do it for myself, but it is still a major battle. My mother's insurance company denied her some basic things while she was dying of cancer and it still makes me sick to think about. I wish all people had access to care, regardless if they had insurance, but I don't believe this will ever occur here.

Most UK doctors don't test for things like EBV. They don't seem to want to give antivirals either. You're usually told to rest up and drink plenty of fluids, then sent on your way again.

Many doctors will not test for EBV if the patient thinks they have ME/CFS but they will test if they suspect actual Mono. They might start with the Monospot test but usually also test for EBV pretty quickly (if they have already ruled out strep).

 

[Luther Blissett]

It is definitely based on ability to pay but the insurance companies will fight to the death to deny you care if you are not a good advocate, and know how to appeal denials, and stay on top of them. And many people are too sick to do this and the insurance companies count on this. I helped others with this as a social worker (before I got sick) so I am more knowledgeable how to do it for myself, but it is still a major battle. My mother's insurance company denied her some basic things while she was dying of cancer and it still makes me sick to think about. I wish all people had access to care, regardless if they had insurance, but I don't believe this will ever occur here.

Actually, describing your system better, it should be 'getting insurance to pay' as you've already paid for it. So sorry for the extra crap you have/had to go through with your mother.

 

[Gingergrrl]

Actually, describing your system better, it should be 'getting insurance to pay' as you've already paid for it. So sorry for the extra crap you have/had to go through with your mother.

Thank you (re: my mom) and it really is true re: our system. You pay a small fortune for the insurance every month, but this is absolutely NO guarantee that they will pay for what the doctor says you need, even if it is just a basic medication from a pharmacy. The hospital (at least 5-6 doctors) said that my mom needed a facility with a specific level of care for her cancer and her insurance refused. We appealed, they denied. We went for the next level of care, same thing. The only thing they were willing to approve was a skilled nursing facility which was not suited for cancer patients. The outcome would have ultimately been the same but she would have suffered less in the process. There are certain lobbies in the US (Pharma, insurance, NRA, etc) that are too powerful to ever change, but I digress and apologize for going off topic.

 

[JamBob]

In Urban areas we usually get matched with a group of GP's. You can see any of them, it's usually more tricky to see a specific one in my experience. You're allowed to ask for a second opinion. There is always the option of private healthcare too, but most choose not to (and private healthcare does not provide emergency medicine).

The difference between our systems is that one is based on ability to pay, the other is supposed to be based on need. The problem we have is getting the 'need' recognised, that's why national guidelines are important. Broadly speaking

That may be how it works in urban areas but in rural areas there is little option for a reasonable "second GP" opinion. If you live in a small village and the only surgery has one or two doctors and they decide to "collude" with each other then you don't have the option of a second opinion.

The gatekeeping and boundary restrictions that make up the NHS are anti-patient in my view and if I were designing a system based on patient need (and not doctors' monopolistic needs) I would choose a system such as can be found in various countries Europe or Asia where any patient can go to any doctor and the money (or insurance) follows the patient and not is not assigned to any given doctor. No choice and no options are fine when you have something very standard that can be dealt with in a paternalistic way but when you actually need help with a more complex problem than can be dealt with by a simple "care pathway" then the NHS is very constricting for patients.

Also the current system has an impact on quality insofar as the GPs have a monopoly over a captive audience dictated by boundaries. They don't have to up their game or maintain good quality because they will always have patients (and an income) whatever the quality of the service provided.

 

[Inara]

So far then there is no reason to get excited about a proposed treatment whose side effects can be serious risk of infection and which might only apply to a very small group of patients.

If I understood correctly the risk of infection can be overcome by giving immunoglobulins. Yes? No? If I understood one of the researchers correctly improvement was significant, at least in some, where autoimmune issues are present - or more precisely, muscanergic and/or adrenergic autoantibodies.

So if the risk can be handled, does there remain a problem?

Sure, one of the problems is that neither Igg nor immunoadsorption are affordable.

The point about that all antibodies etc. are removed and therefore we can't say why immunoadsorption might help in some people with ME is a good point. Still, I can't understand why it is dismissed so easily.

I really do hope we can have a Q&A about this topic...

 

[Inara]

People implied that the lab gave everyone a positive result but this is factually incorrect

I didn't have a positive finding, but one of the antibodies was in a gray zone. So it wasn't negative, too (but not significant).

but I found it very interesting that they were looking at calcium channelopathies which it seems literally no one is researching and I wanted to learn more about it.

I would be interested, too, since a gene mutation was found in my case that may lead to a calcium channelopathy and whose significance is unknown. I wonder if there are others with this or similar mutations.

 

[Jonathan Edwards]

If I understood correctly the risk of infection can be overcome by giving immunoglobulins. Yes? No? If I understood one of the researchers correctly improvement was significant, at least in some, where autoimmune issues are present - or more precisely, muscanergic and/or adrenergic autoantibodies..

No, @Inara, there is no guarantee that you will not get infection during th treatment before it is time to top up its. Since this is an unblinded uncontrolled study we cannot assume any improvement had anything to do with the therapy. This is not adequate evidence. And these antibodies are almost as common in normal people as in ME so we do not know if they indicate autoimmunity of any significance. Moreover with rituximab there was no correlation between having antibodies and improving.

In other words there is no evidence so far that can reasonably be said to. be clinically significant.

 

[Gingergrrl]

The point about that all antibodies etc. are removed and therefore we can't say why immunoadsorption might help in some people with ME is a good point. Still, I can't understand why it is dismissed so easily. I really do hope we can have a Q&A about this topic...

I totally agree with you! I do not dismiss that all of these potential treatments have risks (IVIG, Rituximab, IA or PP) but I would still want to study them much further and isolate the responders to figure out why they are responders? I would love more Q&A on all of this and agree with you that I don't understand why it is so easily dismissed. It is taken seriously on other places where I discuss autoantibody issues (am not talking about PR vs. some other autoimmunity groups) but I know not to push the topic too hard on this board b/c it is a no-go over here!

I didn't have a positive finding, but one of the antibodies was in a gray zone. So it wasn't negative, too (but not significant).

That is exactly what I mean. I know many people who were certain they would be positive on the autoantibodies yet ended up being positive for zero of the nine. And I know people on the full scale of positives 1/9, 2/9 all the way to me (7/9) and Pibee (8/9). I have not found anyone yet who is positive for all 9/9.

I would be interested, too, since a gene mutation was found in my case that may lead to a calcium channelopathy and whose significance is unknown. I wonder if there are others with this or similar mutations.

I would be very curious to find out more about this, too. I don't know if I have a gene mutation but I have the calcium autoantibody. It seems significant if Griffith University wants to study it further and I wish other teams did, too.

 

[Inara]

This is not adequate evidence

Thank you @Jonathan Edwards about clarifying about the risk!

No, it's not evidence - obviously. I know the researchers don't view it like that. It could be a starting point.

At this point, as I see it, there isn't much about ME treatment. So to hear there was a significant improvement in some (I'm referring to what I was told, not to the paper) is something. I totally agree it must be investigated further.

I am also not happy about the fact that it seems that paths aren't taken further. Sometimes you have to walk a mile more to see it's not a dead end...My impression is that "starting points" aren't followed further; including findings of the past - I mean by the researchers. Sometimes it's obvious it will lead to nothing, sometimes it's not.

I also agree that if a finding (or theory) doesn't fit the overall picture it must be rethought or even dismissed. If the overall picture is really known - do we know? In case of ME, I say it isn't. But I think sometimes - or even often? - you need a lot more than "it doesn't fit into the picture"; intuition can fail us sometimes.

I understand that Scheibenbogen et al concentrate on the (possible) autoimmune aspect in ME - and I think that is science. To go deeper. They will either find more hints that there isn't an autoimmune subgroup, or that there is one, or that there's another disease, as others have mentioned above.

It might be clear to some what's the case, like you @Jonathan Edwards who worked on autoimmunity (yes?); maybe it will turn out you were right all the time. (Like in maths when some see the solution at once and some have to think about it for days.) But you could be wrong, too (I cannot say, really! it's not an offense). It seems there are others who don't share that opinion at this point of time, e.g. Scheibenbogen et al. We need more facts.

 

[Mithriel]

It may be a different symptom but people with ME often talk about "air hunger". I do not know if everyone is talking about the same thing, but I have several problems with breathing. There is the physical problem when my chest muscles go into spasms and I can feel as if I have a tight band round me.

More common is during the night mainly (but also at other times) I just feel as if I can't get enough air in. I end up hanging out an open window gasping.

Most distressing is a strange feeling which comes through my sleep which I find hard to describe. I can't get enough air and feel like I am choking. I have to sit on the side of the bed lean forward and try to force air in.

These are all different from the breathlessness of panic and don't worry me as they happen so often.

 

[Inara]

@Gingergrrl, maybe channelopathies play a role in ME, may it due to autoimmunity or gene mutations or whatever - just my guess. It would be interesting to know which ones, if so. E.g. some types of calcium channels play a role in energy metabolism, and their malfunction leads to inhibition of pyruvate dehydrogenase.

And in the ICC primer I found on p. 6 "channelopathy impairments" (this is one reference: https://www.ncbi.nlm.nih.gov/pubmed/10790725 - that paper is certainly known by some).

 

[Gingergrrl]

Thanks @Inara and it sounds like we are interested in a lot of the same topics and research. I know all of this research is in the preliminary stages, like you said, but we have to start somewhere and even the biggest breakthroughs started with a tiny glimmer (unless they got really lucky the very first attempt)!

I think there are a lot of similar and overlapping issues (with autoantibodies, channelopathies, dysautonomia, etc), and someone may start out researching with one specific thing in mind but end up finding another.

 

[andypants]

I have to sit on the side of the bed lean forward and try to force air in.

A tip from my asthma days is that it is usually more effective to focus on breathing out.

When we feel like we can’t draw a proper breath we instinctively try to pull in as much air as possible, however the problem is often that not enough air gets expelled. Then there’s not enough room for fresh air, you feel like you can’t breathe and try to get more into already full lungs.

Try focusing on breathing out for as long as you can, slowly and calmly until there’s nothing more to expel. You can be very sure your body will take care of the inbreath (ever tried holding your breath forever?), so just let it happen naturally and then focus on breathing out again. If you are gasping for air rather than calmly letting air in you probably pushed the outbreath too far

Don’t know if this helps you at all, but it has helped me a great deal

 

[BruceInOz]

Most distressing is a strange feeling which comes through my sleep which I find hard to describe. I can't get enough air and feel like I am choking. I have to sit on the side of the bed lean forward and try to force air in.

Have you had a sleep study? This could sound like sleep apnoea.

 

[Pechius]

I could swear that I read somewhere that autoantibodies have to be somehow activated or actually primed to do damage only when the certain conditions are met, like if some kind of immune cells get activated? I could be talking complete nonsense though... so sorry for that, but I just thought that this would explain why someone with low antibodies has severe symptoms while someone with high ab may not have any symptoms.

 

[Jonathan Edwards]

I could swear that I read somewhere that autoantibodies have to be somehow activated or actually primed to do damage only when the certain conditions are met, like if some kind of immune cells get activated? I could be talking complete nonsense though... so sorry for that, but I just thought that this would explain why someone with low antibodies has severe symptoms while someone with high ab may not have any symptoms.

Antibodies cannot be activated or primed. They just bind to what they like to bind to.

What may be relevant is that the binding in itself does not do much in most autoimmune diseases. (there are exceptions where the antibody binding actually alters pathways.) In order to get inflammation the antibody has to be recognised as having bound by either complement proteins or Fc receptors on phagocytes or killer cells.

There are lots of reasons why the level of antibody measured in a plastic tube need not reflect the power of the antibody to cause symptoms or signs. Nevertheless, to have evidence that the antibodies do anything at all one expects to see some sort of correlation. At present the evidence for autoantibodies of any sort being clinically significantly more evident in ME than normal is not convincing.

 

[sb4]

I was told by several Neuros in 2016 (re: my calcium channel autoantibody) that someone could have a low level but extreme symptoms or a high level and zero symptoms (but with the CA+ Channel auto-antibody, the level should be zero).

I am sure I have asked you something similar before but do you think this can happen in the muscarinic antibodies as well? @Jonathan Edwards What I mean is, I have done the cell trend antibodies test for B1&2 M1-5. All came back very low except M3&4 (like the study showed) which was just below at risk range. Is it possible that although it is a negative, those antibodies are "active" ones, or even the ratio is playing a big factor.

I know I'm clutching at straws here but big symptoms for me are POTS, heart pounding, gastroparesis, and dry mouth. If I remember right M3/4 are, in part, responsible for vascular contractions (POTS/heart symptoms), smooth muscle contractions (gastroparesis), and salivation. All correlate with my major symptoms. Of course it could be a number of other things that affect the same system, maybe even small fiber neuropathy, but what do you think?

Also as to the other discussion going on in this thread, I too don't feel comfortable posting controversial opinions on here.

 

[Jonathan Edwards]

I am sure I have asked you something similar before but do you think this can happen in the muscarinic antibodies as well? @Jonathan Edwards What I mean is, I have done the cell trend antibodies test for B1&2 M1-5. All came back very low except M3&4 (like the study showed) which was just below at risk range. Is it possible that although it is a negative, those antibodies are "active" ones, or even the ratio is playing a big factor.

Anti-muscarinic antibodies are notorious for being pretty meaningless, with regular false positives.

The differences between ME and controls for these antibodies do not at all suggest that they are relevant to symptoms directly. If they were one would expect a much more black and white difference.