Preprint A Proposed Mechanism for ME/CFS Invoking Macrophage Fc-gamma-RI and Interferon Gamma, 2025, Edwards, Cambridge and Cliff

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Nightsong said:
https://web.archive.org/web/2025071.../08/05/gli-affari-del-prof-pio-conti-detto-c/
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Here‘s an english translation.
Biolife is a provincial scam compared to Scientific Reports, the least expensive and most profitable of the open access journals of the Nature group. … recycled the garbage produced by a Chinese paper factory about twenty times.
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What a hellhole of a „scientific journal“:
The article in violation of every code of ethics and human rights produced by racist gynecologists and voyeurs of the State University of Milan and the San Raffaele hospital that I was talking about a year ago when Leonid had reported it to me is finally withdrawn (h/t E.K. Hornbeck).
It took seven years of protests during which the authors defended the ethics of their "Miss Endometriosis" contest.
Anyway, congratulations to Prof. Paolo Vercelliniof the University of Milan, the creator of the competition among his patients: he is even talked about in the Guardian.
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Utsikt said:
Conti’s comment says that he is affiliated with Tufts University, but I can’t find him on their webpage:

Welcome to the Tufts Online Directory

directory.tufts.edu directory.tufts.edu
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This bio from infectiouscongress.com/ mentions the following:
From 1986-2022, he studied the pathophysiology of mast cells at the Molecular Pharmacology and Drug Discovery Laboratory at Tufts University in Boston, directed by Prof. T.C. Theoharides. The studies done in this research center led to the publication of a significant number of articles in the best international scientific journals.
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biolife-publisher.it also mentions that time period.

His former boss, Professor Theoharides, has a website called mastcellmaster.com.
 
Chandelier said:
This bio from infectiouscongress.com/ mentions the following:

biolife-publisher.it also mentions that time period.
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Aren’t those just him saying he worked there? I haven’t found any other sources that support his claim.

But regardless, can you claim an affiliation if you no longer work there? Seems a bit odd to me..
Chandelier said:
His former boss, Professor Theoharides, has a website called mastcellmaster.com.
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That website was a complete nightmare..
 
Chandelier said:
His former boss, Professor Theoharides, has a website called mastcellmaster.com.
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This gentleman recently had a presentation on the Youtube channel of the NSU Institute for Neuro-Immune Medicine on the topic "Science Behind Chemical Sensitivity":



I decided to not watch the video because his homepage where he peddles supplements looks really quacky:

Dr. Theoharides, PHD, MD

www.drtheoharides.com www.drtheoharides.com
 
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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 medication be useful for co-culture experiments, or are there better ways to neutralize IFNγ?
 
wigglethemouse said:
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, an anti-interferon-gamma (IFNγ) antibody medication be useful for co-culture experiments, or are there better ways to neutralize IFNγ?
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1. Well, activation needn't be expansion, though it could be for T cells. I am not sure macrophages multiply on activation. But there are shed loads of T cells in spleen and lymph node and a few more activated ones might be hard to pick out. Nobody has even looked as far as I know. You can't biopsy a spleen.

If it is activation of a small set of T cells that then go off and signal to nerves or brains through interferon (or even to nerves in spleen) I don't think anyone would have seen that. Maybe that's what the lymphocytes in PM dorsal root ganglia were doing.

Circulating cell populations would not necessarily change- although one hole us that they might behave differently in coculture.

2. An anti i Bergeron antibody might be a treatment. Not sure why you would want block IFN in a co-culture. The first thing would be to measure it. The co-culture is to pick up T cell responses rather than macrophages although I guess you could also look for an FcRI expression response lockable with anti-IFN but I wouldn't necessarily predict that.

Interesting questions though.
 
Jonathan Edwards said:
But there are shed loads of T cells in spleen and lymph node and a few more activated ones might be hard to pick out. Nobody has even looked as far as I know. You can't biopsy a spleen.
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Perhaps dendritic cells might be better suited than macrophages for migrating to interact with T cells upon engagement of FcγRI by "junk" antibodies. From what I read they travel to the lymph nodes and spleen to engage with T-cells upon "stimulation".

But then I go back to the recent Cambridge University paper that found both T cells and Macrophages were required for spontaneous IFN-γ release in Long Covid (link).......

My 20mins of google tells me there does not seem to be much literature on the consequences of DC's and FcγRI stimulation specifically.......
 
Sasha said:
This thread has got away from me now but has there been any discussion of how the theory might explain why some many PwME seem to react badly to medications?
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I don't think so, and the hypothesis doesn't cover symptoms.

However I think it's worth more discussion, perhaps it's own thread? I wonder if drug sensitivity could be related to sensitivity to nerve signalling changes. There was discussion that the nerves could be affected by T-cells/IFN-gamma as could dorsal root ganglia neurons expressing FcγRI. @Snow Leopard is very interested in afferent nerves being affected and sensitised. So could changes in meds affect the afferent nerve/brain sensitivity?

The more I think about it nerves and brain signalling are one thing that can bring about the hour to hour fluctuation in symptoms that many experience. There must be a connection.

I don't want to take the thread off track, but I wonder what other diseases experience medication sensitivity - that could be a clue we are missing.

EDIT : Most medication sensitivity searches come back with allergy, liver, or kidney causes. I get the feeling that it could be something more subtle e.g. the disease overwhelming or down regulating the genetic pathways responsible for clearance of drugs, enzymes involved with glutathione, or Glutathione S-Transferases being affected which can also disrupt cell signalling pathways, modulation of the immune system, and ROS in addition to detox.
 
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We have little or no specific information about intolerances to medicines in MECFS. I think they are probably just a reflection of interance of environmental stimuli, and as Utsikt says, neurally mediated. What would yrigger a slight off feeling in a heslthy person triggers majorvproblems for someone with MECFS.

The idea is that this sensitivity is due to priming by gamma IFN.
 
We have little or no specific information about intolerances to medicines in MECFS. I think they are probably just a reflection of interance of environmental stimuli, and as Utsikt says, neurally mediated. What would yrigger a slight off feeling in a heslthy person triggers majorvproblems for someone with MECFS.

The idea is that this sensitivity is due to priming by gamma IFN.
 
Jonathan Edwards said:
We have little or no specific information about intolerances to medicines in MECFS. I think they are probably just a reflection of interance of environmental stimuli, and as Utsikt says, neurally mediated. What would yrigger a slight off feeling in a heslthy person triggers majorvproblems for someone with MECFS.

The idea is that this sensitivity is due to priming by gamma IFN.
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That's interesting. I wonder if that would mean, though, that you'd expect the level of the intolerances to be correlated, such that a person who is very intolerant to sensory stimuli would also be very intolerant to meds, and vice versa. I'm completely tolerant to sensory stimuli AFAIK but have huge problems with some meds.
 
Sasha said:
That's interesting. I wonder if that would mean, though, that you'd expect the level of the intolerances to be correlated, such that a person who is very intolerant to sensory stimuli would also be very intolerant to meds, and vice versa. I'm completely tolerant to sensory stimuli AFAIK but have huge problems with some meds.
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I assume it would just depend which nerves/cells/bits are sensitised. There is a great deal of variation between us. So I wouldn’t expect there to need to be a clear correlation.

I didn’t think I had any medication sensitivities but then found some seem to set me off. Some seems like a more pronounced version of normal stuff people get (nausea etc) which to me is like the body saying ‘new chemical, I may be being poisoned, react’ while others are more clearly neural, like bounceback from certain sleeping meds. I can vaguely get a feel for how it all fits into the overall-responsiveness hypothesis.
 
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