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

[ryanc97]

A few years back I tried to get an understanding years of my own blood tests that indicated NK cell count being extremely low and having some other anomalous immune results from blood tests. I ended up consulting with the head of the immunology department at a University research Hospital. he had spent his whole career in the innate immunity field. he said he only trusted trust any NK tests in the United States that came from one specific university hospital lab. He said he actually re-assayed for three times before he started to believe the numbers.

FWIW, I also remember that Dr. John Chia only would use ARUP for his NK cell testing.

i’m not claiming any expertise in this area. I’m just trying to give you some feedback… This discussion about daratumumab is certainly intriguing…

Well, I find it hard to believe that nobody can test NK cells well in the whole of USA except for one lab.

My take: for his very stringent needs maybe only that lab was good enough for him.

 

[forestglip]

If we suppose that high NK count is related to better antibody dependent cell cytotoxicity, might the fact that the correlation was with blood NK cells provide a clue about where the cells that need to be killed are?

The multiple myeloma studies found correlations with NK cells in the bone marrow, and presumably not in the blood (though maybe that study exists and I haven't seen it), so maybe that's related to needing to kill bone marrow lymphocytes. Maybe in ME/CFS, it's some type of CD38 cell accessible from the blood instead.

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Also, if the mechanism is ADCC, might we see correlations with the other cells that do this? Wikipedia seems to say ADCC is mainly related to NK cells, but macrophages and neutrophils might also be involved:

ADCC requires an effector cell which classically is known to be natural killer (NK) cells that typically interact with immunoglobulin G (IgG) antibodies.[3] However, macrophages, neutrophils and eosinophils can also mediate ADCC, such as eosinophils killing certain parasitic worms known as helminths via IgE antibodies.[4]

 

[hotblack]

Also, if the mechanism is ADCC

That’s been a question I’ve had. Wikipedia quotes a few papers when it says:

Daratumumab binds to CD38, causing cells to apoptose via antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, inhibition of mitochondrial transfer or antibody-dependent cellular phagocytosis.

Do we have a circular argument here that NK cells must be relevant because the mechanism is ADDC and the mechanism must be ADCC because NK cells are relevant? Are other mechanisms just as likely or have I missed something?

 

[forestglip]

Do we have a circular argument here that NK cells must be relevant because the mechanism is ADDC and the mechanism must be ADCC because NK cells are relevant? Are other mechanisms just as likely or have I missed something?

I don't know if it's circular. It's more like NK cells might be relevant because of the study correlation. And ADCC might be relevant if NK cells are relevant. True, there might be other possibilities for why NK cells were significant (including randomness).

 

[ryanc97]

That’s been a question I’ve had. Wikipedia quotes a few papers when it says:

Do we have a circular argument here that NK cells must be relevant because the mechanism is ADDC and the mechanism must be ADCC because NK cells are relevant? Are other mechanisms just as likely or have I missed something?

ChatGPT can give you a good overview of how Daratumumab works.


There are a few mechanisms it uses to attack the CD38 target cells, ADCC is one of them.