Dumb question(s) time.
1. If "junk" antibodies bind to FcγRI on macrophages which then alert T-cells, do the Tcells and Macrophages "activate", and if so why don't we see an expansion of T-cells and/or macrophages?
2. Could Emapalumab (wikipedia link), an anti-interferon-gamma (IFNγ) antibody...
Betty Raman, one of the authors on this study did just that as part of the following study in Long Covid. Maybe the equipment in this study didn't allow for that as it seems from this other study that metabolites can change fast...
I wrote earlier that it was a shame that this paper didn't go back and compare to HC and MS in data from the earlier study so we could interpret it better. In the webinar linked above Dr. Cliff also made the same point and said that they hadn't got the full data yet and would likely do that later.
I went back and watched Dr. Cliff's CureME webinar presentation and I realised that there is an awful lot of overlap between mild/moderate and severe ME/CFS despite there being group differences.
Slide at 40mins
This does not look like two different diseases.
Slide at 39mins
This does not...
I think I understood about 1% of what I skimmed. A shame they took the time to analyse data on HC, FM, ME/CFS, and coexisting diseases, yet the sample gene expression dataset they used was relatively small.
I actually don't know if there are any large gene expression datasets in ME/CFS. I guess...
The PDF of the NIHRIO report can be read on this LINK.
Why was the search starting 2020? Seems very limiting!
ME/CFS has only Ampligen and Daratumumab and maybe some fatigue drugs listed.
I despair that Paxlovid is listed for long Covid as the large trials I've seen report show no benefit...
The updated paper did look at this. Here is Supplementary Table S2 referred to in the text talking about why they think there is no correlation for obesity/BMI with T cell frequencies. Be interested to hear what you think of this.
I definitely recommend reading some Retraction Watch articles and papers from members of the team. When I read some of the writing from Dr. Elizabeth Bik I was convinced about the poor quality of papers.
@Jonathan Edwards Could this paper be relevant for your QEIOS paper if there is another revision? i.e. increased IFN-gamma and a TEMRA T cell type that can be activated without TCR stimulation?
It looks like this paper was reviewed and published on 1 June, 2023 with a new title. Interesting that TEMRA came up again in Long Covid and was highlighted by Dr. Cliff's team at UCL in ME/CFS. Could there be something about TEMRA that is important to dig deeper on? Interesting that these cells...
On one of my first interactions with an ME/CFS researcher they explained to me 95% of research is not replicable. I think the biggest issue they explained was incorrectly controlled methods and sample handling. At the time I think I asked about metabolomics and Seahorse experiments. I was...
The Cliff et al 2019 ME/CFS paper (link to thread) and 2025 paper (link to thread) had findings on CD45RA+ TEMRA cells but I can't figure if what this paper is measuring is exactly the same.
It is interesting though that there is such a difference between mild moderate and severe. The conclusions are that these could be two different diseases.
I was mild/moderate for decades until what seemed like a switch flipped to severe. Did I have two different diseases or did some mechanism...
I find there is too much variation day to day, and somewhat week to week, and month to month, but monthly tracking seems to work well when compared to the previous year (I have seasonal variation). So long term follow-up is really important for treatment studies with minor or moderate effect...
This is a very technical paper that I find very hard to understand. This study is ONLY ME/CFS mild/moderate vs severe to show the differences in T cell behaviour between the two groups.
It really needs to be interpreted together with their 2019 paper (link to thread) which included T cell...
It looks like this work was done at the University of Cambridge, UK. Does anyone have any contacts with the authors to make them aware of how their work may align with the JE et al hypothesis and try and figure out if CureME biobank ME/CFS, control, and MS samples would be suitable for a...
I recommend re-visiting this paper again as it is quite fascinating how they determined CD8 cells and macrophages were the ones needed for unstimulated IFN-gamma release in Long Covid.
Excerpt for Figure 3
Depletion of CD14+ cells reduced IFN-γ release in all cases. However, the isolated CD14+...
Now that the JE et al hypothesis paper (link to thread) is out, which references this paper, I went back and looked at the figures.
Figure 1 of this paper is quite outstanding, especially in relation to the hypothesis.
Legend of figure
(A) We compared unexposed and Long Covid cohorts
(B)...
There was a thread for a T cell vs severity Jan 2025 preprint by Dr. Cliffs team.
https://www.s4me.info/threads/abnormal-t-cell-activation-and-cytotoxic-t-cell-frequency-discriminates-symptom-severity-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-25-lee.42017/
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