NelliePledge
Senior Member (Voting Rights)
Me three
ME/CFS Science Blog article - Immune findings in ME/CFS
- Thread starter ME/CFS Science Blog
- Start date
V.R.T.
Senior Member (Voting Rights)
I am getting really sick of the pessimism that keeps being trotted out over and over again every single time anyone offers the faintest glimmer of hope.
Our grandchildren? We have researchers and clicnians on here most days saying that there is hope for a breakthrough soon and it's met with this endless doomerism.
This is a disease where many people suffering are completely suicidal with despair. Telling people that there is no hope that there will be help in their lifetime is as dangerous as giving them false hope.
I did not mean to state that there is no hope. I certainly have no authority to establish such a position for anyone. I am one of those people who is often suicidal. I often feel frustration with the expectation that I keep my pessimism to myself or that I refrain from stating what I feel is a realistic position. I do my best to maintain hope, and with luck, my fears will be proven thoroughly, embarrassingly wrong. All of this said, I appreciate that their expression has the potential to do harm, so I will delete the post and will do my best to shut up in the future. My sincere apologies for any hurt caused, and I mean that.
Last edited:
V.R.T.
Senior Member (Voting Rights)
No need to apologise (or to have deleted it), I got a bit worked up and maybe posted on the attack. I understand that your fear and pessimism is genuinely felt. I was a very pessimistic person before this and in many ways still am so perhaps I find it harder than most to ignore statements like those you often make. So I end up debating with people who make them, so they make more of them which makes me feel even more despairing...rationally speaking I am fairly hopeful, but I get the fears nagging at me every day still. Anyway I wasn't talking only about your posts and I didn't intend it as an attack on you personally or anything.
I hope you are proven thoroughly wrong too but if so it will not be a cause for embarrassment on your part but celebration!
Thank you for your comments. I appreciate your pushing back on my initial post and your comments here. I did not delete the post in an offended huff, but rather after your response led me to reconsider what it actually contributed to the discussion. I let a little frustration creep into my response and am sorry for that, I think deleting it was the right thing to do.
I will also be the first to admit that my pessimism is at least as much a defensive strategy as it is anything resembling a rational appraisal of the situation. Even independent of our current circumstances, I am sure everyone here has different means of dealing with our situations and what is to come - it is a sad but probably unavoidable thing that our methods sometimes conflict and risk agitating or even harming others. I certainly want to do everything I can to avoid that if possible.
Thank you again. Here's hoping we can both be celebrating sooner rather than later.
Last edited:
ScoutB
Senior Member (Voting Rights)
I think it's normal, in really bad situations, to sometimes just want to be able to describe exactly what is wrong, or what you fear is wrong, and just be heard at least. Maybe a "DHagen vent thread" is a solution? Then folks could choose to read it or not. Though you'd probably have to put a big disclaimer at the top that you just want to be heard, not argued with, we are an opinionated lot...
I'm looking forward to reading this @ME/CFS Science Blog. It sounds as though it is a terrific resource, very useful. I plan to mention it in a meeting later today.
To make progress, we have to stop being stuck in the ruts of what we think we know. 'It's inflammation!' is definitely one of the ruts.
Thanks again @ME/CFS Science Blog.
I guess as usual, the reality is a bit more nuanced e.g. 'it's probably not inflammation, and even if it is, it depends on how you define 'inflammation' and where in the body and when in the disease process it occurs'.
The fact that we haven't found reliable cytokine signals detectable in the blood doesn't mean that there aren't some cytokines acting on a really local scale, for example right next to a neuron. It's the old story of the drunk person looking for his keys under the lamp post. the endless studies looking for cytokines in the blood have been like that.
I thought your post was making an important point, and one I struggle a lot with in advocacy. That is, it is much easier to sell a research programme that promises an imminent cure 'it's inflammation! we have a good plan to fix it!', than to fundraise for more fundamental research. Few people want to hear 'we don't really know much about what is causing ME/CFS right now and we don't have any treatments'; they will ignore people saying that. Instead they will choose to listen to the people in expensive clinics with their menus of drugs or the alternative health practitioner down the road who claims to have cured people.
To make progress, we have to stop being stuck in the ruts of what we think we know. 'It's inflammation!' is definitely one of the ruts.
Thanks again @ME/CFS Science Blog.
MrMagoo
Senior Member (Voting Rights)
Listen these people think it’s that type of “inflammation” that you can cure with stretching and lo carb whole foods…you know, the socially constructed inflammation
+1
The more of my life has been destroyed this disease, the more openly hostile I become to false hope. It is the worst possible response, and both the medical profession and patients need to stop indulging in it.
If there is currently no realistic explanation and effective treatment – and there isn't – then that needs to be openly stated and accepted by all parties, before we can move on to a more realistic response and plan.
Excellent Blog.
I just wanted to throw into the mix a concept that may have some relevance. Immune tolerance, in theory, at least, is a well-established concept, dating back to the 1950's. It's perhaps most familiar in situations involving pregnancies, and I think it received some renewed attention recently as part of the Nobel prize in medicine.
It has nuanced meanings depending on who is wielding it, but one researcher, Finnegan, writes in Sleeper Agent that immune tolerance is "The state of unresponsiveness to a specific antigen or group of antigens to which a person is normally responsive. Immune tolerance is achieved under conditions that suppress the immune reaction and is not just the absence of an immune response"
and
"...early studies of immune tolerance and LCM virus...taught us that a devious infection can be present, actively causing a chronic, slow disease while appearing healthy with no abnormal bloodwork, little to no antibodies or inflammation, but left the victim feeling horrible and incapacitated..."
So, again at least in theory, this may tie back to the observations made about lack of any overt immune signals that might suggest infection or persistence.
DMissa
Senior Member (Voting Rights)
For those who are dillusioned by multiple negative findings in an area, I think that you should instead take it as a sign of progress. For those researchers paying attention it indicates what isn't worth pursuing. With enough of that information in hand, the field of possibilities narrows appreciably. That's a win.
neophyte32
Senior Member (Voting Rights)
You're right, but after speaking with a prominent (and media-savvy) MECFS researcher, he believes that some studies on antibodies or viral persistence were poorly conducted. The problem is that I get the impression we're doing the same studies over and over again.
Kitty
Senior Member (Voting Rights)
Totally. And I think the blog reveals how much and for how long people's thinking has been running along the same rails.
neophyte32
Senior Member (Voting Rights)
Yes, of course. In the scientific timeframe and in the practice of science, it's a positive thing.
The major drawback is for severely ill patients because our timeframe isn't the same. We're more focused on the need for results.
I haven't left my house (even though I have a beautiful garden) since September, haven't showered since August (my poor wife cleans me with a washcloth), and haven't read or watched TV for 13 months. I'm not complaining, no, but I mean it's an impossible situation. Anyway, sorry, I don't want to play the victim, but many people are in my situation.
So yes, proceeding by elimination helps things along, but it's hard to see scientists struggling like this. With the number of studies or time wasted at the OMF, for example, we could have funded SequencEM. Similarly in Germany, I hope the money will be well spent and not just on the obsession with autoimmunity. We need to be pragmatic.
GPCR-aabs, mitochondria, CPET, energy metabolism, NK-cells, viral persistence... the memes seem go in circles with little ingenuity in-between. A lack of fresh ideas seems characteristic.
neophyte32
Senior Member (Voting Rights)
Is it possible to go further without neuroscience?
Or worse, and this is what scares me, do we have the technological tools to understand MECFS?
I have the impression that this disease (if it is indeed a disease) remodels, completely recodes the immune system, and even certain brain pathways. I remember perfectly the moment my body switched off, a sensation so strange that I will never forget it. Like a shock.
The article is right: we need to rethink all of this.
But with neuroscience.
Paradoxically, the fact that this disease is linked to infections might be throwing us off the scent... I don't know.
Dude
Established Member (Voting Rights)
On the topic of antibodies:
Carmen Scheibenbogen once stated that not all patients with high antibody titers are necessarily ill. What matters most is the functional activity of the antibodies.
In the case of GPCR autoantibodies (e.g., against the β2 receptor or M2 receptor), it is not just the quantity (titer) that is important, but especially:
which receptor is targeted
where exactly on the receptor the antibody binds (epitope) what functional effect it has (activating vs. blocking)
Example:
Scheibenbogen et al., Brain, Behavior, and Immunity (2018)
Finding: β2-adrenergic and muscarinic antibodies can be functionally active, independent of their absolute titer.
Heidecke from CellTrend has also pointed out that autoantibodies can act either as agonists (activating) or antagonists (blocking).
This means that two patients with the same antibody titer can experience completely different effects.
For Example:
In Graves’ disease (Morbus Basedow), antibodies activate the TSH receptor. Here, it is not the level alone that matters, but the functional effect at the receptor.
Reference:
“Functional autoantibodies targeting G protein-coupled receptors in cardiovascular diseases” (Wallukat et al.)
Key takeaway:
GPCR autoantibodies can act like ligands → quality matters more than quantity.
Carmen Scheibenbogen once stated that not all patients with high antibody titers are necessarily ill. What matters most is the functional activity of the antibodies.
In the case of GPCR autoantibodies (e.g., against the β2 receptor or M2 receptor), it is not just the quantity (titer) that is important, but especially:
which receptor is targeted
where exactly on the receptor the antibody binds (epitope) what functional effect it has (activating vs. blocking)
Example:
Scheibenbogen et al., Brain, Behavior, and Immunity (2018)
Finding: β2-adrenergic and muscarinic antibodies can be functionally active, independent of their absolute titer.
Heidecke from CellTrend has also pointed out that autoantibodies can act either as agonists (activating) or antagonists (blocking).
This means that two patients with the same antibody titer can experience completely different effects.
For Example:
In Graves’ disease (Morbus Basedow), antibodies activate the TSH receptor. Here, it is not the level alone that matters, but the functional effect at the receptor.
Reference:
“Functional autoantibodies targeting G protein-coupled receptors in cardiovascular diseases” (Wallukat et al.)
Key takeaway:
GPCR autoantibodies can act like ligands → quality matters more than quantity.
V.R.T.
Senior Member (Voting Rights)
I didn't know that. It makes more sense why she's still pursuing them in that case.
Does she have any evidence they are 'higher quality' in MECFS?
Jonathan Edwards
Senior Member (Voting Rights)
This is basic immunology stuff, but the question is whether it is relevant to ME/CFS at all. In all recognised autoimmune diseases there is an imprecise relationshp between antibody titres and pathogenicity but there is still a very obvious difference between normals and patients. In ME/CFS there isn't.
Unless we have some specific data showing that people with ME/CFS have antibodies with specific binding properties this is to my mind a smoke screen. If titres are not what matter then presumably even the small differences noted are of no interest?
V.R.T.
Senior Member (Voting Rights)
This was a really good and necessary article. I really hope it sunk in with some of the people who are pushing inflammation and viral persistance etc.
I did think there were a few notable omissions unless I missed them:
The finding of higher cd38 and cd24 in MECFS B cells.
Jackie Cliff's T cell findings.
The T cell dependant IFNy long covid finding from 2024 that Rosetta Stone may be trying to replicate.
I did think there were a few notable omissions unless I missed them:
The finding of higher cd38 and cd24 in MECFS B cells.
Jackie Cliff's T cell findings.
The T cell dependant IFNy long covid finding from 2024 that Rosetta Stone may be trying to replicate.