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

I find it hard to believe someone with ME/CFS on, say 1000 steps per day just around thier house, would not at least increase to about 4000 steps if they improve significantly and are able to go out more, even if they are doing more brain work.

The problem might come with milder ME/CFS if the pwME is already on 4 to 5 thousand steps per day on better days, as I probably was when my ME/CFS was mild and I was still working part time. Unless I restarted deliberately 'exercising' on getting better, my step count might not increase much.

Just stopping gettting PEM would increase average step count, eliminating all those days of being stuck in bed crashed.
I agree as a severe person who during bad months does 800 — 1500 steps a day, but when am in a good month (recently due to Botox for migraine helping me) can do 2000 to 3000 just around a two bedroom apartment and patio. You can increase steps a lot around the house without leaving when you feel a bit better just doing chores / organizing.
 
Do I understand their view correctly that Rituximab might work if applied long enough so that new plasma cells cannot be formed. If it is applied too briefly like in the phase III trial, the B-cells are targeted but the long-lived plasma cells might still be producing antibodies?

Roughly yes, I think. But plasma cells can last for years and IgG levels stay normal without any replacement in the context of rituximab.
So maybe high baseline IgG4, like high NK cells, might be an indicator of who will respond.
Yes, like the NK finding this is very intriguing - a subset with 4x higher IgG4 respond.
 
I find it hard to believe someone with ME/CFS on, say 1000 steps per day just around thier house, would not at least increase to about 4000 steps if they improve significantly and are able to go out more, even if they are doing more brain work.

The problem might come with milder ME/CFS if the pwME is already on 4 to 5 thousand steps per day on better days, as I probably was when my ME/CFS was mild and I was still working part time. Unless I restarted deliberately 'exercising' on getting better, my step count might not increase much.

Just stopping gettting PEM would increase average step count, eliminating all those days of being stuck in bed crashed.
If I work at home I probably only do 1000 or 1500 steps per day. I was thinking in terms of smaller improvements and where energy gets spent.
 
While IgG4 did go down more in responders, that's probably because it was four times higher at baseline in responders than non-responders. So maybe high baseline IgG4, like high NK cells, might be an indicator of who will respond.

Table 2:
View attachment 26956
I believe that the reason the non-responders in the study weren't reacting wasn't because their NK cell counts were low, which would have prevented the ADCC from functioning as intended. It didn't work because they developed a distinct subtype of the illness that included low NK cell counts and maybe low IgG4 that isn't strongly B cell mediated like in the responders group. Maybe the BCG vaccine can improve their condition like it helps others who have low NK counts.
 
I think one should be careful about not overinterpreting some of the findings (such as the low NK count correlation). From what I can tell none of these things were part of the prespecified outcome measures or protocols so multiplicities/retrospective analysis might be a problem. From what I recall there was a similar retrospective analysis for the Rixtuximab trials (improvement being correlated to certain GPCR-aabs) that never led anywhere.
 
I think one should be careful about not overinterpreting some of the findings (such as the low NK count correlation). From what I can tell none of these things were part of the prespecified outcome measures or protocols so multiplicities/retrospective analysis might be a problem. From what I recall there was a similar retrospective analysis for the Rixtuximab trials (improvement being correlated to certain GPCR-aabs) that never led anywhere.
I agree, if you measure enough things you can nearly always find something that significantly correlates with your non-responders/responders condition.

And those correlations may not even be false positives, but as @zar nola is getting at, there’s no reason to believe they are causative for responsiveness rather than just being an indirect indicator of different underlying biology in the cohort that happened to be measured in the trial.
 
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