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

I think this is exactly what is frustrating to me b/c if we were just talking about a single study, then I understand saying that one particular study was done poorly. But it seems like whether the research is from the US, UK, Norway, Australia, Germany, etc, when I read about it on other boards/groups, there is a more neutral or balanced discussion of both the good and the bad (in my personal opinion of course) and then I come here and it seems like within one or two replies, the consensus is that all of these studies are poor and conversation ends. Whereas I feel there are pieces of ideas from these studies that are of great value to explore further.

I agree and I am not anti-psychiatry or psychology whatsoever when it is done correctly. I worked the final 12 years (before this illness ended my career) as a social worker in psych/mental health. I agree that the methods of PACE were shoddy and this is indisputable. But some of these other studies (Dr. Ron Davis, Dr. Scheibenbogen, Griffith Uni in Australia, etc) are still works in progress and in the very preliminary stages. I think it is far too early to discount them all and they may end up identifying sub-groups or things of real value.

I agree if they are done randomly but if they identify a viral group who is given anti-virals, or an autoimmune group who is given autoimmune treatments, I do not feel this is riskier than forcing someone who is bed-bound into graded exercise therapy where they have a permanent set-back and never recover from it.

I agree that members here are brilliant, and this is often very intimidating to me as a non-science person. I just feel that a lot of the research is discounted too quickly and I wish that were not the case b/c they may discover something by accident that wasn't even what they set out to find and we could miss it!

 

Absolutely nothing you said was disparaging and I did not take it that way at all and always enjoy reading your posts. I am still learning a lot of the common phrases from the UK that we do not use in the US but they are endless LOL.

My science education was limited, too, and everything I now know is b/c of these boards, and my own research, since becoming ill myself.

This all occurred prior to me getting sick and my knowledge of it is very limited.

Not at all and you write well!

Thank you and I appreciate that and will keep commenting

 

I don't think new research studies are dismissed or discussion discouraged on this forum. Studies are critiqued, not just accepted at face value.

As for the four categories of research you appear to think are being wrongly dismissed, I think you should consider them separately as they have been treated differently.

As far as I am aware, Ron Davis's research as such has not been criticised, just that it has not been published and so is difficult to properly assess. The reports to meetings are tantalising but there is nothing substantial yet that we can consider. Judgement is suspended.

The critiques made of Dr Scheibenbogen on this thread put this single study into historical context and so make it easier to understand its limitations. The failure of the Norwegian phase 3 trial on Rituximab treatment of ME make it clear that there is not a significant auto-immune subset, so if her studies hold up, they would be relevant to only a small group of people.

More tellingly though is the fact that the immunoadsorption technique she proposes is not one that has been adopted for treatment of other autoimmune diseases because the effect is short term and carries considerable risk.

Finally the apparent success of her treatment does not actually support her proposal that particular autoantibodies are responsible for ME. The technique removes all antibodies so we don't know why it was effective.

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.

Sorry I have missed discussion of Cell Trend Lab so don't know what you are referring to.

As for the Griffith team, as one who has made trenchant criticism of their abysmal research, I make no apologies. I have never seen a thorough, serious study from this group. They flit from tiny observational study to tiny observational study. Some of these are interesting but we will only know if they mean something when this group does in depth follow-up studies that convince other scientists that here is something here that is worth trying to replicate and examine further.

So far there doesn't seem to be any evidence of substantial studies of underlying mechanisms coming from the group, surely a hallmark of serious research. Instead there is periodic and vigorous beating of the publicity drum to make us think these studies mean something, but it's no substitute for the real thing.

Here is a more detailed post about what I think is wrong with their research.

They have quite a track record now so it is possible to come to a more definitive conclusion about the quality of their research. As far as I recall, everyone on this forum has found it wanting.

With Dr Scheibenbogen we will await further studies, but this first effort does have some obvious problems.

With Dr Davis, we must wait for evidence to assess.

This seems to me a realistic position for a forum whose purpose is to consider the science of ME. I can't see the point in simply getting excited about any research on ME, regardless of quality.

 

With a lot of these preliminary studies, I'd 'discount' them to the extent of thinking that they are not strong enough to alter how I think of the issues around ME/CFS, while still staying open to the possibility that they may lead on to work that identified sub-groups, or things of real value.

I'd certainly hope that some people's criticism of research here would not lead to others feeling put off from saying something positive about it. We want everyone to feel free to post their own views and be able to talk things over.

 

I guess we have to agree to disagree on this one! Also, to clarify, I didn't mean that there were four categories of research vs. that I was just giving four examples that came quickly to my mind.

I remember some very mean-spirited comments directed straight at him but I have no desire to re-hash them. I respect him and his work even if it has not been published yet.

I viewed it differently, that there is a B-cell Autoantibody driven group BUT I do not know if this group will ultimately have ME/CFS or another similar, but different, autoimmune illness. I know it may be a small group of people but I feel this group is still worth studying. If nothing else but to figure out how they are different and pull them out of studies in which they could confound the results (b/c I am pretty sure that I am in that group).

I am not endorsing immunoadsorption (IA) per se versus that it is a mechanism, like plasmapheresis (PP) in which a very quick remission of symptoms (usually followed by relapse) indicates that autoimmunity is the core problem (unless I am totally misunderstanding it). To me, this would be a useful diagnostic tool and give information for future studies. I do not disagree that there is risk but I truly do not know if it is greater risk than IVIG or Valcyte or many other meds that people try. For me, a study could still have value, even if the proposed treatment has risks.

I apologize that I do not have a thread to link to at this time, and some of the discussion might have been on the other board. I just know that many people immediately refer to Cell Trend (the lab used by Dr. Sheibenbogen to test for autoantibodies) as "bullshit" and other derogatory terms. I've spoken to the director of Cell Trend on the phone, as has my doctor, and I have done the testing twice and my results were identical both times and completely matched with my symptoms. I know other people who did the testing and were completely negative. People implied that the lab gave everyone a positive result but this is factually incorrect (and I do not mean you @alicec)!

I do not know much about the Griffith Team 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 do not know if their study design was poor but I was interested in their overall concept or hypothesis that they were researching and think it is worth examining further.

I definitely don't think that we should be getting excited about all research but also want the opposite not to happen (that research is so quickly dismissed as bad).

Thank you and I do feel free to post my own views, questions, etc, and it helps me to learn more since I do not have a strong science background and am the first to admit this.

 

I would like this too, but in order for it to happen it must be baked into the forum rules. Maybe we could exercise our voting rights, so that the silent majority could get a chance to be heard?

I learn a lot by reading different viewpoints. I enjoy reading @Gingergrrl posts. I hope we can encourage other members to post.

 

Then let’s all agree to use our voting rights. It’s been 5 months, since we opened our doors, so how about we vote at 6 months?

 

Thanks @MErmaid for saying that you enjoy reading my posts but I am not sure what you mean re: the silent majority not posting?

I didn't post on S4ME for about 3 months but it was while my mom was dying of cancer and I realized I just could not keep up with two boards at the same time. But it was not b/c of anything that happened here.

I like both boards b/c they are each different and unique. I do feel that new research is often quickly dismissed over here but that would not stop me from sharing my opinion or asking questions.

 

All that those who wish to be heard need to do is post.

 

The problem is that if you look at the data in detail, @Gingergrrl, there is no evidence for any such group. We may be led to think that there is but if there was then the original data from the phase 2 rituximab study would have looked different. Immunology is at least as complicated as working out why your car won't start. You might think the battery is flat but if the engine turns briskly but does not start the battery is not the problem. You can work things out much the same way in immunology and say the evidence just does not point in this or that direction. I spent my life doing this and worked out why rituximab might work in certain diseases and studied where it did. As the same person I can see no good reason to think that we have evidence for there being an ME subset caused by receptor antibodies. The rituximab trial might have picked out such a subset and it did not.

That does not in any way mean that Dr Scheibenbogen should stop looking for autoantibodies and other signs of real immune subsets. Nobody is putting anyone off that.

 

I think there is a culture clash here.

The environment I was brought up in conditioned me to accept and get used to people saying bluntly what they thought. Others are not comfortable with that but i think in a very broad and generalised way, there is a big difference in discourse across the Atlantic. There also seem to be big differences in the acceptance of individual vs group action, the uses and misuses of optimism, experimental treatments, how governments and media treat pwme, along with nationalist discourses and the acceptability and/or usefulness of them.

I wish people would speak up if they want to, they can offer insight from an outside perspective that the in group don't notice.

If people are not going to act in good faith, there is not much that can be done to narrow the gap, and at the same time, it's good and vital for people to ask for explanations and reasons for comments, and good faith should be assumed by default.

 

I really, truly hope that she does keep looking and I believe there is a group of people with autoantibodies causing all kinds of unexplained symptoms from POTS & Dysautonomia to Autoimmune Encephalitis to Paraneoplastic Syndromes. I think this is an emerging field and right now most of these people (at least in the US) are given the "CFS" label and told to F off by their doctors.

I am not sure that I understand although I very much respect your opinion @Luther Blissett. Do you mean between the US and UK or something else? Because there are many members of this forum from Canada, Australia, Germany, etc, too. I think we might just have different opinions re: which research interests us as well as different skill levels for analyzing it's quality.

I am confused who the "in group" are and might be naive but I have never felt there was an "in group"! I am definitely more active on the other board but I really like both of them.

What does this mean? Are we still talking about analyzing Dr. Sheibenbogen's research on autoimmunity (this thread) or something totally different? I think I missed a lot from the three months that I was not posting on S4ME!

 

I'm saying that people view from the experiences and social conditions that they are surrounded by. What is 'normal' in their culture is not always the same in other ones. It's not intrinsicly good or bad, it's just different.

The groups are from the perspective of the user. So, for example, when talking about UK things, the "in group" would be people with experience of the UK who share a similar view. I'd like to hear views from people who are observing from outside the UK system, as they have different reference points and notice things that the in group might not notice.

I'm saying that every user, by default should ideally start from the assumption that other users are being honest and trying to act for the good of the community here. In time they will adjust their views of others by observing patterns of behaviour. This is not to say that everyone should agree with each other, people will always disagree. An example of good faith is your taking my post seriously, trying to clarify what I meant, and then deciding what to do with the reply. A bad faith position would be assuming that I am trying to cause trouble for ulterior motives. (Unless you've observed a pattern of behaviour that leads to this conclusion. Then it would not be bad faith but experiential judgment).

If a person is acting in a way that does not break rules, but we find their personality disagreeable, the best thing to do is stop interacting with them. We can have long threads of people storing previous grievances, and looking for ways to 'win' in arguments, or we can use the 'Ignore User' option.

I would rather people ignore me than be annoyed by me and waste energy being annoyed by me. It would be really weird if I was universally liked, but if I annoy someone, I don't want to force them to interact with myself. In non Internet interactions, we ignore people who annoy us, or reduce interaction with them as much as possible. I don't think using the Ignore User function makes anyone a bad person, but people seem curiously reluctant to use it. They seem to look upon using it as a personal failure or a moral judgment.

In this post I am using 'me' as an example, and not saying that anyone in this thread is acting in anyway towards myself that reflects badly on themselves in any way or form. Any reference to people, fictional or not is unintended. No animals where harmed in the making of this post. Please tip the waitress.

 

@Luther Blissett thank you for explaining these issues so well.

 

Yes, thank you Luther for taking the time to explain all of that! I appreciate it.

 

Thanks for the thanks!

It was a spectacularly long way of saying "Group Hugs, not Group Thugs"

 

Although they were removing all IgG with IA, not only B2, they've picked the participants via high B2 levels (I am not sure is it published what their levels were, but I know person on PR who was participating said he is in top 5% in levels and this is why he was picked).

So with this it means, it could be used to determine who will respond to this therapy. CellTrend antibodies could be completely irrelevant to the disease (especially since Phase II, and likely Phase III Rituximab study didnt find connection), but could correlate, at least in patients with extreme scores, with some other pathological antibodies in this autoimmune subset of patients.
For example for B2, the lab range is >14 Units/ml, but there are some in Loebel (2016) study who had scores 40-50, same with M4, where range is >7 Unit/ml, but some scored up to 80.

Rituximab Phase II had only 30 patients, it might be only 1 or tops 2 that had extreme scores that are seen in n=268 in Loebels study, same with Phase III, who had n=150, not enough to be sure there is at least 10 patients with very high B2.
So in this way, if Scheibenbogen picked 10 people with high scores on B2, that group might not be present in signficiant number in any Rituximab study.

Of course: 2nd group of pwME who are negative for B2, would be necessary in study.
and 3rd, sham/placebo group.


For me personally this is not convincing, with 8/9 positive CellTrend, plus positive Sjogrens and Hashimoto, I am still not convinced I am autoimmune subgroup.
Wish there is somewhere I could read about T cells autoimmunity, as this is so rarely used and discussed.

 

Hi @Pibee, we've been discussing this on the other board but you brought up some really good points here (and I know many people no longer read the other board) so I want to reply.

I think this is a really good point, that Dr. Scheibenbogen selected patients with very high B2 levels on testing. I think I know who you are referring to but will not say the person's name to maintain their privacy.

This is also a very good point IMO and my B2 was 18 (so definitely above the 14 cut-off but not ridiculously high). And my M4 was 27 which is much higher than the 7 cut-off. I also know that autoantibody levels do not always correlate with symptoms. 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 not sure if this is the same concept with the Cell Trend autoantibodies, or with autoantibodies in general? I know with my two Hashimoto's autoantibodies, I have had times they were in the thousands and other times they went so low they were almost negative.

I understand what you mean and I do not know if there will ultimately turn out to be an autoimmune "subgroup". For me, it is the overall concept that is important vs. the terminology. I view it as either ME/CFS will have an autoimmune subgroup, and if so, then these studies are very important in identifying it and leading to additional research. Or the alternative that ME/CFS does NOT have an autoimmune subgroup and in that case, we need to identify the responders to autoimmune treatments (like high dose IVIG, IA or PP, Rituximab, etc) and realize that they are a misdiagnosed group, possibly with a completely different illness, and then pull them out of the ME/CFS research so it does not confound it, which benefits everyone IMO.