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A screen like this will probably not ever get sufficient funding for a replication attempt. It’s just seen as a hypothesis generating exercise, so if already done once no funding body sees the point in doing it again (even the very rare private funds specifically for replication)

Epigenetic, not genetic. You’d either see if you can interrupt whatever is maintaining the epigenetic change, or block the main downstream effects of it that mediate symptoms.

I’m well aware of all this, and like I said several times, the specific constraints of being a subtle enough problem to evade all previous screens and investigations, fitting the specific clinical features of ME/CFS where they diverge from general fatigue and unwellness of other antibody...

I think we’re talking at cross purposes?

That supports my point then. I’m saying that if someone wants to hypothesize ME/CFS as an antibody mediated disease, theyre effectively hypothesizing that there’s a magic antibody that only creates malaise/flu-like feelings as in ME/CFS and not any other recognizable phenomena from any other...

That would be my thought as well, or a stably upregulated transcription factor (which would probably be epigenetically upregulated itself). There's a protein complex involved in mediating the interferon response that I've been very interested in--ISGF3 (containing STAT1, STAT2, and IRF9). It's...

There would have been some general pain-related items in the DSQ-SF and a pain-related subscale on the SF-36 but the trial results only report an overall score from the questionnaires, as far as I'm aware.

Apologies @MelbME, I meant the question somewhat facetiously--I used to be in a rheumatology lab and am pretty familiar with this already. My point was that you can't use VH4-34 as an example of why its plausible for a gene like CD38 to be induced globally in B cells by an antibody-mediated...

In LC? Yes, pain and balance issues from Akiko's study

I agree with Jonathan there, cross-species Ig transfer is pretty messy. If there was a very very clear phenotypic difference that strongly resembled ME/CFS (as much as you could get from an animal model, anyways) then maybe it would warrant a further look, but I’d still be pretty skeptical.

I wouldn't agree with Jonathan's assessment there that it's completely defunct--just from my university I know of a couple cases of patients receiving pretty apparent clinical benefit. But it is rarely used since there's no justification to even try it unless the patient is in critical condition...

I wouldn't agree with that, but obviously I'm biased

Sure, like I said before, you can always say that antibodies behave weirdly and heterogeneously and therefore you can't disprove their involvement. What I'm looking for is evidence for which "antibodies-mediating-disease" is the most plausible explanation. People getting better after...

And someone correct me if I'm wrong--the trials of plasmapheresis have been pretty disappointing, right? I find it difficult to reconcile how we'd have a lack of miracle improvement anecdotes from pwME who had 90% of their antibodies removed, even just in the short term, if antibodies mediated...

yes that is your response every time haha

1) CD38 induction in this paper was not a subtle shift visible only if you knew where in the body to look. 2) could you point me to the evidence that VH4-34 is globally induced in B cells by the disease state in lupus other than through the expansion of autoreactive clones? Otherwise it’s not...

But also globally primed B cells for CD38 induction ex vivo

Sure but in those cases we see progressive tissue damage and [edit: constant] differences in immune populations even just doing a single cell screen of circulating or local cells at the site of damage. My point is just that we have no apparent sign whatsoever of any abnormality that can be...

What is hard for me to reconcile about this proposed higher CD38 induction —> more plasma cells problem is that it would only make sense if you also had a magic mechanism like in the Fcgr1 hypothesis explaining how the antibodies themselves, once produced by these plasma cells, invoke a response...

meaning increased prostaglandin signaling -> decreased interferon signaling