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Beautifully put. As a non-scientist learning about MR even I suspected there are no known genetic variants likely to directly predispose to cheese-bingeing. But you have expressed it beautifully.

I asked Google's Gemini 2.5 and it told me the paper says: "2.1.2. GWAS of CFSThe summary data for CFS (ebi-a-GCST006764) were obtained from the IEU GWAS database." ... I cannot for the life of me see that in the paper! nor in the Supplementary Information here ... and if I enter that...

89Zr-PET seems capable of at least lighting up tissues where IFNg is gathered: https://pmc.ncbi.nlm.nih.gov/articles/PMC10735274/ (admittedly in mice). I know nothing about imaging, but maybe some useful techniques are just around the corner. I was interested to see just how much has already...

Are there any direct PET tracers for IFN-γ or other markers upregulated by IFN-γ? To see where IFN-γ is occurring?

The penny has finally dropped, I think: immune "molecules" can activate or amplify signals in sensitized nerves near (for example) degenerated discs.

I am shamefully ignorant about nerves, but: a) what about sensory innervation of structures near the DRG (e.g., spinal meninges) b) what about innervation of the blood vessels supplying the DRG I mis-described it - apologies - please see #313 above for a more considered description, of...

As I say in my post #313 above, my wife experiences "nausea"/"weight" not "pain". Her sensation is an infallible prelude to PEM over 25 years, and there are no other co-morbidities or explanations. Innocent correlation does not seem to me to reflect her evidence.

Here is her typical PEM sequence: a) a feeling of "nausaa" in/around DRG at vertebra prominens (years ago there was also "weight" here, but less so in recent years); not vomit-nausea, rather malaise b) MUST lie down pretty much immediately as her body feels like it will not support itself, not...

Potential DRG involvement keeps tapping at my skull: my moderate-25years-in pwME wife ALWAYS starts PEM with an ache/heaviness in the DRG somewhere around vertebra prominens. Is there good information somewhere about DRG possible involvement?

@Jonathan Edwards, and your co-authors, a huge thank you. PWME I know, including my moderate-25+years-in wife, are so grateful for this huge effort and dedication - it gives them hope (in an indifferent world) to see such a clear framework woven from the evidence/hints so far. Setting the scene...

That interferon/ISG-expression could make PWME feel lousy must lead somewhere, surely? Itaconate-driven peroxiredoxin5-inhibition could surely trigger ISGs yet leave interferon undetectable? Apologies but the concrete reality of "feeling lousy" keeps tapping away at the window.

a) could the hypothalamus be the "brain stem centre"? b) or are there more likely candidates? c) what other inputs (perhaps IFN1s ?) might also contribute to such a signal-integration glitch?

Does lack of "specific evidence" suggest: a) if his theory were true we should have seen evidence of it by now; or b) we should avoid weaving his theory into any hypotheses until such time as it is evidenced?

How about Phair's itaconate-shunt, which he suggets (Janet Dafoe video #1) “burns” (inside glia mitochondria) your neurotransmitters?

Are Jarred Younger (eg his YouTube #15, #14) thoughts about microglia unlikely?

2 more-recent additions: https://pmc.ncbi.nlm.nih.gov/articles/PMC10756525/ https://www.mdpi.com/1422-0067/24/13/10582

I am undoubtedly one of many who would find that fascinating ...

Very very helpful - thanks so much. Although the review is encouraging I am very conscious of:

That's REALLY helpful - and very clear - thank you so much. Watching , in response to Yehuda Shoenfeld at 34:36 "... should we not learn from Charite researchers who looked at long-lasting plasma cells and made no breakthrough to help fight SLE ..." Fluge cites a review article pulling...

Given LLPCs express CD38 but not CD20, and given LLPCs are largely responsible for sustained antibody production, a non-scientist like me is curious to know why the RituxME study did not try something like Daratumumab instead?