Ongoing research: Identifying viruses in tissue and nerve samples from ME/CFS patients

[SWAlexander]

this is why alignment is important

Yes, very important. What kind of alignment are you referring to? Surgical or physio-therapeutic?

 

[Inez]

This sounds pretty exciting to me. Dr Andrew Shaw hypothesises that ineffective/ the wrong antibodies are created for some reason, leading to viral persistence and eventual immune exhaustion. His company Attomarker have created finger-prick test which shows these 'antibody gaps' and is in effect a diagnostic test for long covid. He says he has used COVID monoclonal antibodies to treat one long covid patient in UK and they got much better.
If he's right, I would like to try all the monoclonal antibodies to all the viruses as I have no idea which triggered my ME!

 

[Violeta]

Low natural killer cell function. Many studies on this. Nothing done on it other than acknowledge it. At a minimum it could be helpful to use as a biomarker for diagnosis along with the traditional cfsme criteria.

TGFβ drives mitochondrial dysfunction in peripheral blood NK cells during metastatic breast cancer​

https://www.biorxiv.org/content/10.1101/648501v1

Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome​

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1350-1

The main finding of this study is that plasma levels of the three TGF-β isoforms were equal in a large group of adolescent CFS patients compared to healthy controls. In addition, within the CFS group, plasma level of all TGF-β isoforms were associated with plasma levels of cortisol and urine levels of catecholamines, and these associations were related to fatigue score. Finally TGF-β3 might partly mediate an association between plasma cortisol and downregulation of some B cell annotated genes. These latter observations should be addressed in further studies aiming at unraveling the complex causal interplays between neuroendocrine signaling, subtle immune alterations and clinical symptoms in CFS.

 

[Violeta]

TGFβ drives mitochondrial dysfunction in peripheral blood NK cells during metastatic breast cancer​

https://www.biorxiv.org/content/10.1101/648501v1

Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome​

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1350-1

I don't know how responsible arachidonic acid is for the cascade.

https://www.sciencedirect.com/science/article/pii/S0006497120591106

 

[Violeta]

I don't know how responsible arachidonic acid is for the cascade.

https://www.sciencedirect.com/science/article/pii/S0006497120591106

I might not need to find the answer to that, just take the boswellia.

"Boswellia species contain more than 200 bioactive compounds [110]. Among them, boswellic acid (BA) is shown to have appreciable antiinflammatory activity. The major targets of BA are the members of the arachidonic acid cascade, proteolytic enzymes, oxygen radicals, and the complement system."

 

[Violeta]

I might not need to find the answer to that, just take the boswellia.

"Boswellia species contain more than 200 bioactive compounds [110]. Among them, boswellic acid (BA) is shown to have appreciable antiinflammatory activity. The major targets of BA are the members of the arachidonic acid cascade, proteolytic enzymes, oxygen radicals, and the complement system."

Oh, boswellic acid actually stimulates the release of arachidonic acid, however:

https://pubmed.ncbi.nlm.nih.gov/16788089/

"it inhibits the transformation of arachidonic acid to leukotrienes via 5-lipoxygenase but can also enhance the liberation of arachidonic acid in human leukocytes and platelets."

I was confused when I saw this study all over twitter saying that arachidonic acid lowers inflammation.

Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting​

https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00028-7

Mechanistically, AA inhibits phospholipase C activity to reduce JNK1 stimulation and hence NLRP3 activity. These data show that AA is an important physiological regulator of the NLRP3 inflammasome and explains why fasting reduces systemic inflammation and also suggests a mechanism to explain how nonsteroidal anti-inflammatory drugs work.

 

[forestglip]

Why is one person active at 100, and another one is sickly and dies at 21? We're all different. I expect we have quite different immune cells and immune support systems and levels of support chemicals in our serum, so we do respond differently to different invaders. Maybe having a certain strain of viral infection at age 7 makes for a different immune response to EBV at age 28 than if it was a different strain at 7. For that matter, maybe it makes a difference if you had chicken soup on the third day or on the fourth day. Our bodies are not like consumer products, built from near-identical parts in identical configuration.

Also, while we may know that our cells involve HLA or whatever, there are probably other critical factors that we still don't know about (and have acronyms for). Even if you studied all there is known about immune cells, there's no guarantee that you could find the answer, because it might still be unknown.

Why did I suddenly lose a critical gut bacterial strain? I didn't take antibiotics or any other obvious cause. It's just one of those mysteries. Hey, maybe I picked up a virus that attacked that bacterial strain ... and the virus died out after eliminating its host. How to prove it? Actually, I don't really care, since the problem is now fixed.

I think it's almost certainly a genetic susceptibility combined with some modern environmental trigger like diet or toxins in air or food. If it was just genetic, prehistoric humans with ME/CFS would have probably died out long ago, as it is a majorly maladaptive trait for survival.

My hope is that this trigger is something ongoing and removing it reverses the disease, and not something that happens when you're younger and permanently changes you.

But I think it is very important to put significant resources into looking for what this trigger is.

 

[Wishful]

I don't think we're held in the ME state by an ongoing trigger. I think it's a feedback loop we're locked into, with our bodies adapting to changes to keep us in that state. Normally, homeostasis keeps us in a healthy state, but if something changes the "maintain this value" value, it will hold us in that new state, which may result in symptoms. Changing that value or feedback value is not easy. I've had several treatments that did snap me out of the ME state temporarily, so it is possible to affect it, but the loop adapts to the treatment to make it no longer work. Finding a way to reset us to the healthy state and keep us there needs a different treatment.

 

[hapl808]

I don't think we're held in the ME state by an ongoing trigger. I think it's a feedback loop we're locked into, with our bodies adapting to changes to keep us in that state. Normally, homeostasis keeps us in a healthy state, but if something changes the "maintain this value" value, it will hold us in that new state, which may result in symptoms. Changing that value or feedback value is not easy. I've had several treatments that did snap me out of the ME state temporarily, so it is possible to affect it, but the loop adapts to the treatment to make it no longer work. Finding a way to reset us to the healthy state and keep us there needs a different treatment.

I've had one thing 'snap me out' in 25 years. After not taking antibiotics for 15 years, when I first took Zithro my symptoms went away for almost a week. That's the only time I've ever experienced anything close to remission, and I was mild or mild-moderate at the time (which felt awful with constant GI issues and crashes because I was trying to live a full life).

Nothing has helped much in the last 10+ years.

 

[Wishful]

Nothing has helped much in the last 10+ years.

Well, I didn't say it was easy. I just said that it's possible to snap out of ME. While that doesn't mean that it won't take long to find a treatment, it does mean that treating ME doesn't involve multiple organ transplants or a "take this 4x/day for 20 years before it will show an effect" drug. ME is probably one little chemical switch, but it's a keyed switch with a difficult-to-crack tooth pattern. However, if you do manage to get the pattern right, you can simply switch ME off, immediately.

 

[Norwegianlad]

I've had one thing 'snap me out' in 25 years. After not taking antibiotics for 15 years, when I first took Zithro my symptoms went away for almost a week. That's the only time I've ever experienced anything close to remission, and I was mild or mild-moderate at the time (which felt awful with constant GI issues and crashes because I was trying to live a full life).

Nothing has helped much in the last 10+ years.

Interesting. My dad, who has had ME/CFS for 25 years + as well, also said he once, many years ago, was on antibiotics for a while because of some other thing (not sure what) and also almost felt complete remission.