Passive transfer of fibromyalgia symptoms from patients to mice, 2021, Goebel et al

The author in research recommendations 'Anecdotal evidence from patients with co-morbid FMS treated for their rheumatological condition with biologics including anti-cytokine agents, or B-cell therapies suggest that FMS condition may not readily respond to these therapies; independently, the situation in axial spondylarthritis may be more complex, as in this condition fulfilling FMS criteria may not necessarily mean that FMS is truly present, and the symptom severity score may be a better measure [35]. More systematic understanding of these issues is required to avoid potentially futile trial efforts. ' so he knew that rituximab didn't work probably why he mentions' old fashioned' methods like apheresis.

One thought I had, does this mean fibromyalgia can be detected in autopsies?

And why has nobody replicated this yet? It seems easy to me and not time consuming as a layman, the cell culture test that is

https://www.biorxiv.org/content/10.1101/2022.06.29.498149v1 this one says neutrophils are the cause. Either they're all wrong or this is an establishment of multiple mechanisms?

Also if antibodies bind to nerves, does that mean they stop flowing around the body?

 

I've found an anecdote about somebody feeling better after donating plasma. This is exciting

 

I'm confused. This paper is not in preprint. It was published in June 2021. It's now 2023. The author suggests procedures that lower Antibody circulation may be good treatment. I was initially doubtful, because there was nothing, nada about any anecdotes, nobody with fibromyalgia has tried immunoadsorption or plasmapheresis, but then I realised plasma donation is the same as plasmapheresis. Transfer of human antibodies is not the first time to be shown here, it was recognised AFAIK 10 years ago in other illnesses, giving mice the Antibodies of sick people made the mice sick with the same symptoms! The author is trying to set up a trial to test immunoadsorption. Autoantibody pain that doesn't cause inflammation is NOT a new phenomenon. This paper is not the first to demonstrate it. I can't remember all that I've read but I feel strongly that one cause of fibromyalgia must be due to these antibodies. But there will be many I'm sure.

 

I don't want to preach because I am not an expert, but I please ask you to go read through the history so you can make a judgement yourself, the author Andreas Goebel started publishing about non inflammatory autoantibodies causing pain in 2016. He has now shown this phenomenon through passive transfer is 5 conditions, CRPS, FMS, Long covid, Rheumatoid Athritis, and chronic post-traumatic limb pain. These types of autoantibodies are even in cancer apparently. I don't have enough effort to dig deeper. I do note the sample size is tiny, but it's an objective finding I believe. The SFN neuropathy is linked here, injection into mice led to reduction in IENF density, interestingly another paper also found this. One hypothesis is that all fibromyalgia patients have SFN, but that is not detectable. SFN seems difficult to diagnose as well, not one test is enough. And the symptoms of SFN and fibro are difficult to distinguish. It all seems linked. But IENF density reduction is non specific, as its found in other illnesses too

 

1. It is not pre print! It is published and peer reviewed! You're looking at the old paper lol. Unless you're talking about the neutrophils.
2. The donation of plasma imo seems likely it would always make you feel worse off, that's the most common side effect it'd be Wierd if somebody felt BETTER, right?? It's basically immunosuppressive. Why would a placebo happen instead of nocebo?
3. Yes, is not inflammatory and does not respond to immunosuppressants, but it responds to LDN for whatever reason. And now we have an anecdote of it responding to the physical removal of immune components? Idk how to describe it. Even if fibromyalgia isn't autoimmune, it 'likely involves inflammatory processes' - Jared Younger. Also note this, the Antibodies are not inflammatory they don't trigger any inflammatory response, or not much I think .
4.Let's just drop the fibromyalgia term for a second, let's called it unexplained chronic widespread pain. The connotations are different yea. What I wanna really ram home is not that guys this is it!!! But rather guys, this might be something!!!! A coincidence is worth looking into, it seems lots of drugs end and discoveries are circuitous. It's how bc007 got its start, and I think LDN had the same start. An accidentally discovery, that looked like coincidence.

 

I don't actually think there is any significant similarity. Donation of a pint of blood, including plasma, (maybe even a litre) will not produce any noticeable change in antibody levels immediately, just a change in volume. Even when plasma volume is restored after a period of hours the Ig level is unlikely to be reduced by more than 10%, which is unlikely to be relevant.

For the first hour, certainly, there is going to be no real change in antibody levels.

 

Wait sorry, why wouldn't donation not immediately reduce IgG, only plasma volume?

 

As I understand it, the removal of blood is not going to change the concentration of what remains.

The blood volume will be reduced of course, but it’s the concentration of the blood components that’s important.

 

Can you give me a source of the 10-15% for low dose naltrexone? From the younger studies, the number is 70%~ that have a(not necessarily effective) response. I see what you're saying now though, but I've yet to dig into the numbers. Do you know where I can find them

'The percentages of participants who exhibited at least a
30% reduction in pain levels was very similar between
the two studies, with a 57% pain response rate in the
current study and a 60% response rate in the previous
study'
How do I find the raw data? This is what I've found

 

Keela this is plasma donation though, not blood donation.

 

Heeeey a kiwi! So gatchaman, it would reduce IgG then immediately?

 

Regarding the staining of cells by Antibody not having a pattern and just being brighter, I have no clue if I'm being an idiot asking dumb questions bc I'm a layman, or if this is relevant. And I quote
'Additionally, new insights and the term ‘autoimmune pain’ have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. ' extracellular domains of antigens? Nodal synaptic structures? Pretty sure I'm being ignorant here but wanted to check.
Also you say it's brighter, and that specific staining isn't like that. Could it be similar to how 20% of healthy people have ANA positive? But few of them have strong positives/titres. Thus brighter could be explained?

http://dx.doi.org/10.1136/jnnp-2018-318556

Additionally, Andreas Goebel the author of the Antibody study showed the same process is occurring in rheumatoid arthritis, but in a different manner.
https://doi.org/10.1016/j.autrev.2021.103015
And another link I can't help but wonder, if this is why fibromyalgia patients do not respond to immunosuppressants, is that RA patients with fibromyalgia are less likely to respond to DMARDs. I haven't got access to the last paper, unable to read it
https://doi.org/10.1007/s00296-019-04506-2

 

Mmm okay if anybody has a source it'd be nice. Because I've never heard this number before, only heard 70%. I remember a quote from Geneva Liptan somewhere on the Internet about 70. I looked through the Younger paper, could not find raw data. Or didn't understand it. Or looked too fast. I don't mean to be abrasive and I get it if you don't want to parse through research again, that's the same thing that's stopping me lol I don't want to a few hours for something trivial, LDN was just an aside. But, I should say when one has a claim, the burden of proof should be with the claimant lol, but it's algood. And I should note too, there are two trials!! Both involving 100 patients and LDN, one is going on in Denmark still recruiting last I saw and another in Mexico(sorry no its Spain) by Younger and Co I believe(nvm its by someone else) . I may be mistaken or misunderstanding though. Honestly I appreciate that anybody is even replying to me lol and entertaining my views/ideas

 

Apologies. The question seemed to relate to Jo’s post above the question I quoted - and that was talking about removing blood including plasma.

 

Yes, if the plasma is removed by aphaeresis then the gig level would fall a bit, but to that much, as SNT says.

 

I think we need to inject some realism here.
I have never come across a case of fibromyalgia, either in practice or presented as a case, with symptoms of neuropathy (other than maybe coincidental carpal tunnel syndrome or whatever).

They are not similar.

The invocation of neuropathy seems to be based on the symptom of tenderness, but the tender points are local, not generalised as in neuropathy, moreover I think they were shown to be non-discriminatory and removed from the diagnostic criteria.

Looking at PubMed I have seen no real interest in the 2021 Goebel paper other than from Autoimmunity Reviews, which is the opposite of a recommendation. Goebel has subsequently published 'position' papers with the hallmarks of hype (I will not be specific in case I get charged with defamation).

If anybody was taking this seriously then there would be reports of patients with fibromyalgia treated with rituximab. Rituximab usage has fallen during Covid but tens of thousands of people were already treated, at least hundreds of whom should have had fibromyalgia according to the figures banded about. Rituximab might not work for these putative antibodies but I wold expect there to be some discussion of experience.

I regularly see Maria Leandro, who with me introduced rituximab to rheumatic disease, and I have heard nothing from her about interesting new evidence in fibromyalgia.

 

Evidently I cannot hold a candle to the excellent (informed) posts above. My eyes glaze over somewhat when I hear "autoimmunity" trotted out as a cause ----. It seems to have been tested for (rituximab). I do wonder if GWAS [DecodeME] may pick up a characteristic "autoimmunity" signature i.e. if it were a common cause of ME/CFS --- bit worried about sub-groups making it difficult to identify cause(s).

 

They're not similar? Okay I was under the impression they were, because if say 50% of fibromyalgia patients have SFN, why were they diagnosed with fibromyalgia? That was my logic.
You're right about realism, but I want to beat this horse and flesh it out. Because that's all that can be done until somebody else replicates this. I do think that there is hype involved, that was my initial impression. Is he reeling us on the hook? It seems like such a convenient explanation doesn't it.

Re 'If anybody is taking it seriously', why would hundreds of fibromyalgia patients have recieved rituximab? Rituximab is a high risk drug right? I find it difficult to even obtain Low dose naltrexone, so this would be difficult for me to understand the inner workings. Are you referring to patients with secondary fibromyalgia being treated with rituximab? Jesus christ, I just realised you said you brought rituximab to rheumatic illnesses. I feel embarrassed now.

From my perspective, a layman's perspective, gosh I must seem so pretentious for arguing back, if nobody is taking it seriously, that doesn't necessarily mean the wisdom of the masses is right, right? Just because science is not recognised, does not mean it is wrong. Just that is not recognised. Wishful thinking but, the area of fibromyalgia seems ripe for revolution.
But why is there such disinterest? Could you explain from your perspective if you were researcher reading this, why wouldn't this be remotely interesting? Could it just be a disinterest in fibromyalgia in general?

My final question would be, what is your take on non inflammatory auto antibodies in general? Just the Goebel paper alone made me skeptical. But Goebel was not the first to publish on passive transfer of IG to mice, nor the idea that non inflammatory auto antibodies can cause pain. Is this whole idea all fringe stuff or what. What about his other papers?
One interesting thing I don't know if it is known:CRPS has the same auto antibodies as long covid/cfs/me:adrb2 and m2 receptor

'in regards to B-cell ablation approaches - no efficacy signal on
concomitant FMS has been reported, to our knowledge from trials con-
ducted in RA or Lupus - similar as with some established antibody-
mediated conditions available B-cell ablation methods may not effec-
tively reduce pertinent pathogenic antibodies which will continue to be
produce by plasma cells or by B-cells residing in privileged environ-
ments' just adding this for context from autoimmunity reviews paper. I have no comment.

Also, https://doi.org/10.3389/fimmu.2018.00835 this paper said B cells may stay in inflamed tissue and they resist treatment, is this somehow linked to your idea that auto antibodies are self perpetuating?