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

[forestglip]

I'm I'm not misremembering I think the NK cell findings here were somewhat related to illness duration (I'm not actually sure if anyone checked whether the correlation between response and NK count was stronger than response and illness duration), which would make that quite possible (people with long-term illnesses "responding" better for whatever reasons).

I don't see any individual level data for illness duration in the study. Just a mean and range in Table 1. And I don't see anything about NK relationship to duration. Maybe it's from a talk?

 

[EndME]

I don't see any individual level data for illness duration in the study. Just a mean and range in Table 1. And I don't see anything about NK relationship to duration. Maybe it's from a talk?

Possible, but probably more likely that I might be misremembering. I guess the table does at least suggest the possibility for a relationship.

 

[ryanc97]

Whose theory would be?
OK, it has been the received wisdom in generic immunology circles for decades, but it has nothing much to recommend it.

I think you will find forum members are up to speed on the other stuff!!

Theory from Olav Mella in his video or presentation that was recorded at Charite MECFS conference 2025.




See 14:28.

If it were a common theory, this is the first ever attempt at targeting the source of AABs, which I find odd.

 

[ryanc97]

According to F/M theories in the video: we know LLPCs can live for decades.

I wonder if the faulty LLPCs are a result of a one-time impulse (the CFS trigger event) or the B-cell differentiation process itself is faulty, which means even if you get rid of the current batch of faulty LLPCs with Dara, new faulty ones will come online.

If the latter, then it makes sense to do a course of Rituximab first, to clear your B cells, then do a course of Dara.

Would be nice to know how the 6 responders are doing now.

 

[ryanc97]

"Furthermore, IgG4 production by antibody-secreting cells can be markedly shorter lived than for other IgG subclasses, requiring continuous input from newly differentiating B cells. Indeed, rituximab (anti-CD20) therapy for B cell depletion has been shown to be particularly beneficial in autoimmune diseases characterized by pathogenic IgG4 (auto)antibodies" The unique properties of IgG4 and its roles in health and disease.

And when rituximab was used in ME, it didn't help, even though SLPC was affected by the drug. And as you said, "Rituximab should work if the source is SLPC in theory." In reality it didn't work. Maybe the target wasn't correct, or they didn't use the drug in the optimal way in the study.

I think IgG4 makes sense because it's a blocking antibody and it's known to be noninflammatory and does not activate complement or ADCC, and there are no signs of inflammation or autoimmune tissue damage in ME. It can bind to some of the many proteins that we don't recognize yet as a target. for example, like in MuSK myastenia gravis.

The other question is why the disease hasn’t come back after stopping datratumumab if dara isn’t touching B cells?

Why new autoreactive plasma cells weren’t made

That's what Im trying to figure out. Is it a one-shot impulse style thing where during the CFS trigger, B cells went rogue?