Trial Report Plasma cell targeting with the anti-CD38 antibody daratumumab in ME/CFS -a clinical pilot study, 2025, Fluge et al

[Utsikt]

Yes, there is a post where ME/CFS is compared to lupus somewhere above (Too tired to be able to find it again)

That might have been what’s covered in this long thread

Often people with ME/CFS were originally diagnosed with CFS criteria that are broader and have an emphasis on fatigue. Now CFS is also more and more called ME/CFS. Nowadays the Canadian Consenus Criteria are the gold standard. But so many patients have been diagnosed before that shift in perception and definition of ME/CFS.

I have a friend who has had a CFS diagnosis, which has now transformed to an ME/CFS diagnosis. However, even though her fatigue is much more debiliating than mine (moderate-severe) she could go on working remotely for many years and has just stopped recently. At the same time I don't recognize ME/CFS main symptoms like flu-like feeling, sore throat, atypical headache, neurological problems in her at all.

Will talk to her now!

CCC requires PEM. If someone doesn’t have PEM they’d probably not get the diagnosis today.

But the criteria aren’t that important because we don’t actually know which symptoms that are key in ME/CFS because we don’t know how it works. I’d be more concerned about missing treatable conditions, and if the plausible ones are excluded - does it matter if it’s X or Y if you can’t do anything about it anyways?

There is a thread about missed diagnoses here.

To be honest, I have no knowledge at all about the immune system.

I barely do either and whatever little I learn seem to be gone the next day..

 

[PageofME]

We really aren't ready for a drug to work. The bulk of patients can't get a diagnosis because there aren't services to do it and GPs wont read and follow the guidance and there is currently no one to send patients too who would do this, the existing clinics don't have the right people to deliver any treatments. Even if this was assigned to Rheumatology they have no experience recognising ME/CFS. The entire pipeline is broken from beginning to end, there is no pathway and no place to put that pathway easily to at the moment.

I think it would takes years for this to become available and then it would be only really available to a minority who had got private diagnoses that their GP had agreed to accept onto their records and refer them onwards and the few where their GP/ME service had diagnosed them officially. Until the guidelines are being routinely adhered to I don't see anyway most patients can even get into such a treatment even if they do know what they are suffering from and put into a pathway for this treatment. Every single stage of this needs extensive new training, across the entire country and there is not a single expert to teach them.

That sounds awful. In Switzerland the situation is different. If you're still able to leave the house and are able to stand your ground in front of a dismissive doctor and bring a copy of a document teaching the state of the art of diagnosing and managing ME/CFS you will find a GP sooner or later who will help you get diagnosed. Either they do it themselves. It's not difficult. Or, if they prefer, they will send you to a specialist. A list with specialists is regularly updated by our patient advocacy organisation. The list has been growing fast over the last couple of years.

If you're too sick you need someone who advocates for you. But they can achieve the same for you, I suppose.

 

[PageofME]

At this point my hunch is that the cell count indicates the dysfunction level as well. So you really need a high count or boosted NK cells to get something out of Dara.

To me this is the case because the doses are small compared to MM dosing where they can do like weekly Dara over the course of 6 months. So in theory the NK cell effect might be more important because of the small dose whereas in MM the amount of Dara thrown at the patient just ends up working.

What makes it even worse is that Covid has shown to impact lymphocyte function. So those with repeated Covid infections in the trial probably might have poor NK cell function overall despite enough counts. And that could confound things.

Now if only they decided to boost NK cells via Anktiva for patients before giving them Dara....

Could you present a link to the study or studies that show what kind of lymphocyte damage Covid induces, please?

 

[PageofME]

Be careful about boosting NK-cells.
I think I don't get the flu-like symptoms when in PEM because of low NK-cells.
I won't try boosting the cells unless it is proven to be helpful; if and when treatment becomes available.

May I ask whether you have ever felt flu-like during an acute episode at all? Are you now severe and the flu-like feeling got weaker the more ill you got?

With which criteria have you been diagnosed? I wasn't aware that you can get a diagnosis without a flu-like feeling as the main symptom of illness episodes in the first place.

PEM is required indeed and a very important charachteristic of ME/CFS because it can be clearly distinguished with it from other diseases. However, PEM is not a primary symptom. It rather points to the fact that the main symptoms like a flu-like feeling, a sore throat, an atypical headache, neurological dementia-like symptoms, exhaustion get worse after exertion or that overexertion (relative to baseline) leads to a flare-up of these symptoms.

How would you characterise your main symptoms? Which concrete symptoms get worse after too much exertion?

 

[Kitty]

I wasn't aware that you can get a diagnosis without a flu-like feeling as the main symptom of illness episodes in the first place.

I don't think it's necessary for diagnosis, and not everyone gets 'flu-like symptoms in PEM. It's clear from discussions here that the most prominent symptoms of PEM vary quite a bit between individuals.

 

[PageofME]

I don't think it's necessary for diagnosis, and not everyone gets 'flu-like symptoms in PEM. It's clear from discussions here that the most prominent symptoms of PEM vary quite a bit between individuals.

Indeed, it is not required in the CCC. Although in such a case you have to present autonomic and endocrine symptoms both alternatively to fulfilI the criteria.

I am curious to know more about the symptoms of people without flu-like symptoms because I doubt that I have the same illness with the same pathomechanism as patients who do not experience a range of symptoms from what's called the immune symptom group of the CCC. Feeling flu-like with a sore throat, tender lymph nodes ect.

When I rest well immediately from the start of a flare-up and manage to keep the episode really low intensity – and without having it going up to the brain to provoke inflammation feeling in the frontal lobe – I can't distinguish ME/CFS from a cold. It's only when I get up and do too much after the symptoms have subsided and provoke a relapse by overexertion (PEM) that I understand that it's an ME flare and not a cold.

So for my group the immune symptoms are the lead symptoms and all the other required main symptoms fatigue, problems with sleeping and pain followed only when for some time at the height of my illness (before diagnosis and information on energy management) I was a lot worse and had my first two episodes of 2-3 months and later with only learning to pace had one relapse after another in very short time.

I think that this is a very interesting discussion because I was convinced from my first episode that I had a form of a herpes reactivation because it felt so similar to HSV-1 reactivation. And now I have a herpes drug that I use during a severe episode to avoid more brain damage that suppresses all my symptoms fully. Thus I can not only prevent more brain damage but also damage to the eyes. The more severe my ME/CFS episodes the more severely I get inflammed vessels in the eyes which then often burst (typical also for herpes eye infactions). My eye sight has rapidly deteriorated over the first years of the illness with a pathological development that my optician told me was normal for 60 years old. I had just turned 40.

I find it interesting that there are at the same time other patients who believe that their illness can impossibly be caused by a virus and compare their disease experience to an autoimmune disease like lupus. Time will tell but I think that maybe there is a fundamental problem with the CCC that they still allow that different diseases are conflated.

 

[Jonathan Edwards]

I find it interesting that low NK cells pop up here in this discussion as a charchateristic of ME/CFS. When I referred to an overview paper in another thread that pointed to the main issue in the immune system in as a problem with NK cells when discussing HHV-6B theory as the driver of ME/CFS it seemed that everyone here believes that there wasn't a problem with the NK cells – not at all.

If you hang around here you will get to see that people comment from a wide range of knowledge backgrounds and that we are all trying to navigate a lot of myths put about by so-called ME/CFS experts that turn out to be based on one off observations or otherwise shaky data.

About twenty years ago it was claimed that NK cell levels were low in ME/CFS, or maybe that their function was low. NK cell assays are notoriously difficult to get consistent and to interpret even if you have results. The London CureME group set up a systematic project on immune cells under Prof Eleanor Riley, who is the leading NK expert in the UK. As far as I know they could not confirm any abnormality. Prof Riley moved on to Edinburgh and Jackie Cliff focused on other cells that looked more interesting. I genuinely think that if there was a significant problem with NK cells this team would have found something.

 

[Jonathan Edwards]

Reading through this discussion where everyone seems to believe that the cause of ME/CFS is autoimmunity I wonder whether there is a problem with people with undifferentiated connective tissue disease being misdiagnosed with ME/CFS.

One or two people here believe ME/CFS is autoimmunity but I think most of those of us with an immunology background probably don't. jnmaciuch doesn't and I personally doubt it is typical autoimmunity. We do think it might involve an abnormal immune response though.

Undifferentiated connective tissue disease is generally recognisable by things like marked Raynaud's phenomenon, antinuclear antibodies of various sorts and specific types of joint or muscle problem or entrapment neuropathies. There is often fatigue but it is reasonably easy to identify as autoimmune. Misdiagnosis in either direction no doubt occurs at times - maybe most often ME/CFS is misdiagnosed as an autoimmune disease because the ANA is positive incidentally.

 

[Turtle]

May I ask whether you have ever felt flu-like during an acute episode at all? Are you now severe and the flu-like feeling got weaker the more ill you got?

With which criteria have you been diagnosed? I wasn't aware that you can get a diagnosis without a flu-like feeling as the main symptom of illness episodes in the first place.

PEM is required indeed and a very important charachteristic of ME/CFS because it can be clearly distinguished with it from other diseases. However, PEM is not a primary symptom. It rather points to the fact that the main symptoms like a flu-like feeling, a sore throat, an atypical headache, neurological dementia-like symptoms, exhaustion get worse after exertion or that overexertion (relative to baseline) leads to a flare-up of these symptoms.

How would you characterise your main symptoms? Which concrete symptoms get worse after too much exertion?

So you doubt my diagnose?
I've had ME/CFS for 34 years, since 1991. Was diagnosed a few years later. In 2008 and 2020 I was diagnosed again by the publishing Dutch ME/CFS researchers.
In CPET only 1minute 28 of aerobic energy and not even 40% VO2max + chronotropic intolerance.
Measured on tilt table test with doppler -25% CBF. No POTS or dOH
No Killer cell (reactivity) CD4/CD upside down. Very low acethyl carnetine.
Thyroid trouble
Is that enough to be diagnosed with ME/CFS?
Next time you want to ask these kind of questions please consider being on the receiving end first.

 

[forestglip]

With which criteria have you been diagnosed? I wasn't aware that you can get a diagnosis without a flu-like feeling as the main symptom of illness episodes in the first place.

The IOM criteria, which many studies, including DecodeME, use, doesn't require a flu-like feeling. From DecodeME:

For genetic analyses, we used case inclusion and exclusion criteria based on the Canadian Consensus criteria and/or US Institute of Medicine / National Academy of Medicine criteria for ME/CFS (5,26).

Edit: The criteria from the NICE 2021 guidelines doesn't require flu-like feelings either.

 

[Jonathan Edwards]

PEM is required indeed and a very important charachteristic of ME/CFS because it can be clearly distinguished with it from other diseases.

I don't think we actually have a basis for that. PEM usefully distinguishes people with ME/CFS from those who are fatigued and who do not otherwise have a clear diagnosis. But if there is another diagnosis that symptoms can be attributed to ME/CFS is excluded anyway and nobody bothers to think about whether the symptoms would fit for 'PEM'.

 

[rvallee]

Just to prospect of getting lots of people off benefits and into the workforce should make the politicians prioritise it. Ironically, as soon as people start recovering, there will be more force behind the advocacy efforts as well..

I genuinely trust politicians to do the smart thing here more than I trust the medical advisers who would tell them what is the smart thing to do to put it accurately. As long as the smart thing is in the form of "this will save X billions per year", which is a pitch they already got and bought whole about the "behavioral disorder of perception spread throug the TikToks, or whatever" mumbo jumbo.

Because before the politicians hear accurate things about what's the smart thing to do, the people who have been saying a bunch of nonsense will have to be bypassed and their influence removed, and that's almost everyone. It would take a complete silver bullet for health care systems to turn around once they have something that works. Egos rule.

As otherwise where does it even begin to make sense for people to pay for the solution to a problem that barely exists, not when there is this giant problem where so many disabled people struggling with mental illness are breaking the system and all they need is a little coaching and pestering the "just right" way?

That's where decades of mislabelling chronic illness as mental health breaks the whole system from working rationally. It just keeps raising the bar needed to solve the problem, while lowering it for all the things that amplify its harmful consequences.

This problem is a lot like the root problem with those ethical dilemmas: it's never clear what choice is actually made. In real life such dilemmas almost never exist, there is always mostly uncertainty about what the facts even are, what the impacts of doing one thing vs doing another. Real life is never "you can sacrifice this one person to save a hundred" dilemmas, it's always so murky that setting into motion the things that end up destroying thousands of lives simply to preserve the egos of a few mediocre charlatans can always seem like a good ethical choice.