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

[forestglip]

I don't know whether people with autoimmune diseases such as RA or MS can donate blood/organs and I'd be interested to know if so, why, and if not, why not.

Multiple Sclerosis

We are very sorry but sadly you are not able to donate blood.

This is either for the safety of yourself in giving blood or for the safety of patients that receive your blood.

Rheumatoid Arthritis

You may donate as long as:

You feel fit and well

You have no associated heart, Lung or Kidney problems [...]

 

[Sasha]

Multiple Sclerosis


Rheumatoid Arthritis

That all seems a bit random and mysterious!

 

[Jonathan Edwards]

But if your theory is correct, would our ME/CFS be transmissible in blood and should we continue under a ban on that basis?

No.

 

[Andy]

blood.co.uk says you can’t donate if you «feel ill» and that you have to be «generally fit and well».

I think that excludes anyone with ME/CFS.

Who can give blood

Find out more about who is eligible to give blood. You should be able to give blood if you are fit and healthy, weigh over 50kg and are between 17 and 65. Men are able to give blood every 12 weeks and women every 16 weeks.

www.blood.co.uk

It also says
"There are other medical conditions that may mean you can't donate.

Visit our health, eligibility and travel section for a full list, or give us a call on 0300 123 2323 to check if you can donate."


If you follow that link and look up CFS then it says,

"CFS : Fatigue
If you have been diagnosed with any of the below conditions unfortunately you will be unable to donate;

Chronic Fatigue Syndrome (CFS)
Myalgic Encephalomyelitis Syndrome (ME)
Post Viral Fatigue Syndrome
Systemic Exertion Intolerance Disease (SEID)"

 

[Sean]

Not allowed to donate blood here in Australia. Which I agree with as a reasonable precautionary measure.

 

[Annavive]

Abstract:
Evidence bearing on possible mechanisms for the clinical syndrome of ME/CFS is reviewed. The evidence is used to argue for a hypothesis that centres on a form of persistent, inappropriate, ‘neuroimmune hypervigilance’ mediated primarily by T lymphocyte-macrophage interaction but influenced by IgG antibody binding to the gamma interferon-inducible high affinity immunoglobulin receptor FcγRI. This proposed mechanism could explain why the illness resembles post-infective T cell-mediated autoinflammatory syndromes in age of onset and time course but has a female preponderance similar to autoantibody-mediated disease.

Link | PDF (Qeios preprint, May 2025, open access)

Does this mean interferon gamma is bad for us? I have wanted to try interferon gamma before but after seeing this that seems like it may worsen symptoms

 

[Jonathan Edwards]

Does this mean interferon gamma is bad for us? I have wanted to try interferon gamma before but after seeing this that seems like it may worsen symptoms

I cannot think of a reason for someone with ME/CFS wanting more IFN gamma. It is a mediator of feeling bad. The last time I heard of people being treated with T cell cytokines in a pilot drug trial they all got very ill and I think one died!

 

[neophyte32]

Very interesting. I hadn't read this work before. The only drawback, or rather, the frightening element: the limited therapeutic options. If anti-CD38 doesn't work, I imagine there's nothing left for years. I'm 41 years old, a father, and have a very severe form of the disease (it actually started in April 2023, with a prodrome in January 2022, and has been very severe since March 2025), and I think that, unfortunately, Daratumumab won't work for me. It's hard to stay optimistic. Oh well, I lost the lottery of life. But it's a very interesting theory for future patients or those with a more moderate form.

 

[Jonathan Edwards]

The only drawback, or rather, the frightening element: the limited therapeutic options.

As indicated in the paper this is less a proposal for a preferred theory than an exercise in theory-building. And if this theory is roughly right there ought to be T-cell inhibiting strategies to find. Nor does it discount a success for daratumumab by any means.

 

[neophyte32]

As indicated in the paper this is less a proposal for a preferred theory than an exercise in theory-building. And if this theory is roughly right there ought to be T-cell inhibiting strategies to find. Nor does it discount a success for daratumumab by any means.

Thank you for your reply. Yes, but it will take at least 10/15 years to find a suitable T-lymphocyte inhibitor for MECFS. Then, of course, we have to consider the research time, which is always too long for severely ill patients like me. I'm definitely focused on myself, haha. In any case, thank you for your work.

 

[Kitty]

Yes, but it will take at least 10/15 years to find a suitable T-lymphocyte inhibitor for MECFS.

I'd be surprised if it took that long, given that these drugs are used in other diseases. The problem at the moment is that we don't know what the underlying problem is, but once we do the prospect of a treatment gets a lot closer.

 

[Creekside]

I cannot think of a reason for someone with ME/CFS wanting more IFN gamma.

Back when my ME started (before I knew about ME), I probably would have tried supplemental IFN-g if it had been cheap and readily available. the purpose would have been to test whether IFN-g was involved in my symptoms. Since the symptom flares from what I believed was IFN-g rise 24 hrs after exertion faded quickly and reliably, popping an IFN-g pill would have seemed safe.

Testing things that you theorize will make your symptoms temporarily worse is a valid scientific technique for testing the theory. Not pleasant, but, for example, it would be good to know for sure that chocolate made your symptoms worse before giving it up forever.

 

[Kitty]

for example, it would be good to know for sure that chocolate made your symptoms worse before giving it up forever.

Eating chocolate's hardly in the same bracket as messing with your immune system.

 

[Utsikt]

Testing things that you theorize will make your symptoms temporarily worse is a valid scientific technique for testing the theory.

Lots of unethical or very unwise things are valid scientifically. Doesn’t mean we should do it.

 

[V.R.T.]

this is less a proposal for a preferred theory

I know you don't have a preferred theory per se, but what possible mechinisms do you find particularly interesting right now?

 

[Jonathan Edwards]

I know you don't have a preferred theory per se, but what possible mechinisms do you find particularly interesting right now?

All the ones we are discussing.

 

[Creekside]

Lots of unethical or very unwise things are valid scientifically. Doesn’t mean we should do it.

Lots of experiments are bad ideas, but many are good ones too. In my example, I'd experienced years of IFN-g rise due to exercise, with no lingering effects, so duplicating that rise with a pure sample if IFN-g would seem to me a safe way of testing whether the symptoms were due to IFN-g or not. To test my response to cumin, I tested other spices that contained the other compounds in cumin. I didn't manage to get any perilla (also contains cuminaldehyde) before I stopped getting PEM, but I would have tried pure cuminaldehyde as a reasonably safe experiment if it had been readily available.

I've tested many things that I predicted would make my symptoms worse temporarily, because I felt that the knowledge gained was worth more than the tiny risk that it wouldn't follow the usual (many, many times replicated) pattern of just temporarily making the symptoms a bit worse. There were also many experiments I rejected, because I judged the gain vs risk was too low.

Where would science be if we raised the threshold for acceptable risk? That has consequences just as reducing the threshold for acceptable risk.

 

[forestglip]

I cannot think of a reason for someone with ME/CFS wanting more IFN gamma. It is a mediator of feeling bad. The last time I heard of people being treated with T cell cytokines in a pilot drug trial they all got very ill and I think one died!

Discussion after the above post regarding interferon and Dr. John Chia has been moved to the thread: John Chia - Clinician/Researcher

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

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Thank you for the reply! Could you link the study mentioned, did these patients have ME/CFS? That is highly concerning, and I do not think I will pursue any treatment with IFNγ.

I suspect this information listed below is why ME patients still are interested in interferons.

Information Taken from Phoinixrising on interferon Link: https://phoenixrising.me/treatment/...ng-chronic-fatigue-syndrome-mecfs-interferon/

Dr. John chia reports
“Interferon alpha/delta – Eight of 14 severely ill ME/CFS patients with enteroviral RNA in their blood returned to work on a half or full time basis after interferon alpha/delta therapy but most relapsed several months later. Heavy exertion was a common relapse trigger. Some patients responded well to another course of interferon”

“Interferon alpha/gamma – One patient receiving interferon alpha/gamma three times a week returned to full-time work two months later and was well for 14 months when she relapsed. Another patient had a similar response. Dr. Chia reported that eight of 14 severely ill ME/CFS patients with enteroviral RNA in their blood returned to work on a half or full time basis but most relapsed several months later.“

These patients all had severe ME/CFS. To go from bedridden to full time work is quite an extreme improvement, even if the patients didn’t permanently stay at those levels after the treatment

 

[ME/CFS Science Blog]

Bit of a long shot but was speculating that if the neural pathway that induces symptoms is constantly on, even without the cytokines that normally trigger it, then perhaps artificially raising the 'feeling bad' cytokines such as interferons might help to reset or recalibrate?

If ME/CFS pathology is mainly in the nervous system where we can hardly measure or influence it at this point, then trying to influence or reset it with immune therapies might be worth considering?

There was a small RCT of alpha interferon in the 1990s but it didn't found an effect
alpha-Interferon treatment of patients with chronic fatigue syndrome - PubMed

 

[EndME]

Bit of a long shot but was speculating that if the neural pathway that induces symptoms is constantly on, even without the cytokines that normally trigger it, then perhaps artificially raising the 'feeling bad' cytokines such as interferons might help to reset or recalibrate?

Why should this not happen as part of ordinary infections?