You probably have an autoimmune disease...

sometexan84

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@Wishful how about now?

(2020) Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset

Solid size study: 305 ME/CFS patients and 201 healthy controls

Autoimmune genes in ME/CFS (specifically those triggered by infection) vs Controls and vs other ME/CFS
(PTPN22 rs2476601: OR 1.63, CI 1.04–2.55, p = 0.016; CTLA4 rs3087243: OR 1.53, CI 1.17–2.03, p = 0.001)

"The associations with PTPN22 and CTLA4 SNPs point to a role of autoreactive T and B cells in the pathomechanism of ME/CFS"

"Our findings prompt us to intensify research into autoimmune mechanisms and perform clinical studies with drugs targeting autoreactive B cells"
 

sometexan84

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A recent study found that only two cytokines working together may be responsible for the severe effects of covid - TNF-a and IFN-y. This finding may offer insight into potential treatment for covid and autoimmune diseases.

https://www.sciencedirect.com/science/article/pii/S0092867420315427#:~:text=TNF-α and IFN-γ Induce PANoptosis,damage through inflammatory cell death.
You know, you may be on to something here. I found this 2001 article in my notes that shows the same thing.

Circulating tumour necrosis factor-α and interferon-γ are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

Also, the high IFN-y seen in ME/CFS is often associated increased severity.

https://me-pedia.org/wiki/Cytokine#Table_of_Cytokines

1608766826697.png


TNF-α is usually higher in ME/CFS regardless...

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I found this 2001 article in my notes that shows the same thing.

Circulating tumour necrosis factor-α and interferon-γ are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

Also, the high IFN-y seen in ME/CFS is often associated increased severity.
Yes, that seems to be the case.

TNF-a could be more important than IFN-y. Some of the covid supplements mentioned in the clinical trials are: quercetin, zinc, melatonin, berberine, and black cumin seed oil. These supplements have in common the inhibition of TNF-a, while increasing IFN-y. Perhaps meaning the deleterious effect of increasing IFN-y is outweighed by the benefit of decreasing TNF-a.

In contrast, selenium has a favorable action on both TNF-a and IFN-y. There are posts on PR about using selenium for ME/CFS. These studies mention selenium's positive effect on both TNF-a and IFN-y.

"Selenium treatment significantly inhibits tumor necrosis factor-α-induced cell death and tau hyperphosphorylation in neuroblastoma cells."
https://pubmed.ncbi.nlm.nih.gov/25109896/

"Selenium prevents interferon-gamma induced activation of TRPM2 channel and inhibits inflammation, mitochondrial oxidative stress, and apoptosis in microglia"
https://link.springer.com/article/10.1007/s11011-020-00624-0

There is a lot of information on these cytokines at:

https://selfhack.com/blog/supplements-lifestyle-factors-influence-tnf-interleukin-6-il-6/
 

Learner1

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I actually tried plasmapheresis earlier this year. I did 4 plasmaexchanges in 1 week. I was positive for 3/4 of celltrend Antibodies + Tpo-antibodies. The result: I had no improvement at all.

That’s why I don’t believe that antibodies play a major role in this disease, at least in my case. Beside my case I know at least 2 other cases who did plasmaexchange and immunadsorption with positive antibodies and no improvement.
I'm aware of a couple of cases of people with multiple B cell antibodies who were helped by plasmapharesis shirt term. It gas to be repeated though. Others are helped with IVIG or Rituximab.
ivermectin stimulates the production of antibodies, via a mechanism involving T-cells.
antibodies are made by B cells.
I knew anything which could stimulate antibody production, as he has hypogammaglobulinemia, which results in low levels of antibodies and immune weakness.
Hypogammaglobuinemia is a lack of immunoglobulins, which are made by B cells. Gammaglobulins, in the form of SCIG or IVIG are a treatment for those of us with this condition. Colostrum and a few commercial supplements also provide gammaglobulins.

One big factor that can reduce production of Immunoglobulins is infections. The body can't keep up the production when fighting and can go into a slow downward spiral, so figuring out what the body is fighting, and going after that, while supporting antibodies can make a big difference.
 

bread.

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The problem with plasmapheresis and immunoadsorption, is that it seems to often be a temporary fix.

The good news is that this type of treatment has shown great symptom relief. The bad new is, symptoms often return.
Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME

Removing the antibodies won't fix genetic autoimmune susceptibilities, nor will it remove infections that cause the production auto-antibodies, or repair the immune system.

I'll check out some of those autoimmune herbs and what not you mention. I'm definitely interested in supplements that can aid in this area.

A top priority should be gut optimization. Optimizing your gut health, and bacteria diversity will boost your host-cell immune defense and adaptive immunity. Not to mention balance out cytokine production, reduce inflammation, inhibit the colonization of pathogenic microbes, and promote regulatory T cell development and function.

I know about 10 people with me/cfs that had plasmapharesis without any improvement - Dr. Scheibenbogen very clearly has a financial motivation to find some kind of auto immunity in me/cfs.
 

Learner1

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I know about 10 people with me/cfs that had plasmapharesis without any improvement - Dr. Scheibenbogen very clearly has a financial motivation to find some kind of auto immunity in me/cfs.
I am thankful for Dr. Scheibenbogen's work, which is supported by others. Finding a cause of my autoimmunity and that I had autoimmunity led me down a path to improve symptoms.

Just having ME/CFS does not mean one has autoimmunity, and if one does not have B cell antibodies making mischief, then plasmapharesis would not be helpful. Additionally, it may remove antibodies that are needed to fight an infection, and do could be counterproductive. There is no substitute for thoughtful and comprehensive testing to tease out the specific problems an individual patient has and treat them appropriately, and taking into account situations where treating one problem can be counterproductive to another.

Making blanket statements about a particular treatment across all ME/CFS patients is not really useful as we have a variety of different problems driving the same symptoms and making accusations against a researcher without basis is not helpful.
 

Wishful

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@Wishful how about now?
Still on 'I'm awaiting further research'. ;)

The research is interesting, but it doesn't directly link the autoimmunity effects with ME. It might indicate that some people are more susceptible to infection triggered disorders that in turn are more likely to trigger or help sustain ME or make the ME more severe.

If we had a reliable marker for ME, we could improve our understanding of study cohorts. We could, for example, see that some correlations might be with severity of ME rather than its existence. This study's correlation might only be with PWME who are severe and who triggered on a specific virus. Other people in the cohort might have the ME marker, but lack the SNPs or other indicators of autoimmunity.
 

bread.

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I am thankful for Dr. Scheibenbogen's work, which is supported by others. Finding a cause of my autoimmunity and that I had autoimmunity led me down a path to improve symptoms.

Just having ME/CFS does not mean one has autoimmunity, and if one does not have B cell antibodies making mischief, then plasmapharesis would not be helpful. Additionally, it may remove antibodies that are needed to fight an infection, and do could be counterproductive. There is no substitute for thoughtful and comprehensive testing to tease out the specific problems an individual patient has and treat them appropriately, and taking into account situations where treating one problem can be counterproductive to another.

Making blanket statements about a particular treatment across all ME/CFS patients is not really useful as we have a variety of different problems driving the same symptoms and making accusations against a researcher without basis is not helpful.

How would you know that it has no basis?
 

Wishful

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My recent experience might be of interest in this discussion. A few weeks ago I started feeling significantly worse a few days after a trip to town (plague pit!!!). I also got much worse symptoms, particularly brainfog, after eating protein-rich foods. My hypothesis was that I'd gotten an asymptomatic viral infection, which was keeping my IFN-g high, resulting in high conversion of TRP to neurotoxic kynurenines via IDO in microglial cells. That remained until I took some elderberry gummies, and a couple of days later, those extra symptoms were gone. Obviously, I can't repeat the experiment multiple times to verify it, but it certainly looks like elderberries either allowed my immune system to eliminate the virus or it 'reset' it in some way.

I'll leave figuring out what that might mean in terms of immune system function and autoimmunities to those who have studied those in more depth.
 

sometexan84

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antibodies are made by B cells.
Yes, and ivermectin stimulates the production of antibodies by B-cells, via a mechanism involving T-cells.
Yes, T-cells play an important role. Antigen priming of autoreactive T-cells stimulates B-cells to produce the antibodies.

Peripheral tolerance helps control this. If tolerance is broken, the autoreactive T-cells can cause autoimmunity.
 

sometexan84

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I know about 10 people with me/cfs that had plasmapharesis without any improvement
It sounds like you are assuming auto-antibodies are the sole cause of symptoms. And that if plasmapheresis does not improve symptoms on someone, then autoimmunity is not involved in their set of conditions.

I am suggesting that autoimmunity is involved in the onset and/or perpetuation or exacerbation of "ME/CFS". How your specific set of symptoms and conditions evolve from this could make treatment very complex.

What if you have constant fatigue from cancer, or anemia, or a thyroid disorder, fibromyalgia, sleep apnea, disease or injury to brain/liver/heart/kidneys, some type of neuropathy, or about 20 things that end in "itis"....

I mean, any of this could cause major symptoms. Most of these won't be automatically healed by plasmapheresis. And all of these can be due to autoimmunity.
 

sometexan84

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I was diagnosed with "ME/CFS".

But before I knew what that was, I had other testing done and was also diagnosed w/ Sleep Apnea and Hashimoto's.

Maybe I will do some Rituximab, or plasmapheresis, or immunoadsorption, or some form of autoimmune treatment like that. And maybe I will feel much better (a lot of maybes, I know).

But what if I never found out that I had (2) other conditions that can cause extreme fatigue? Maybe I'd get some form of autoimmune treatment, and I'd still feel like shit because I wasn't aware of other conditions I had.
 

Hip

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Synthesis and biological evaluation of berberine derivatives as a new class of broad-spectrum antiviral agents against Coxsackievirus B
Interesting, but a long way from clinical use, unless one were willing to organize a custom synthesis of these compounds, and willing to take them without any animal and human testing.

It would also require that the bioavailability and protein binding of these compounds allow sufficiently high in vivo concentrations to match the in vitro concentrations.
 

Learner1

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Yes, and ivermectin stimulates the production of antibodies by B-cells, via a mechanism involving T-cells.


See this study.
This is what the study says:
Antibody production against sheep RBC, a T lymphocyte-, macrophage-dependent response, was enhanced by ivermectin treatment (P = 0.00049). In contrast, antibody production against dinitrophenyl-Ficoll, a T lymphocyte-independent, macrophage-dependent response, was not altered by ivermectin treatment. Results indicate that the immunostimulatory properties of ivermectin are associated with altered function of T lymphocytes, in particular, T-helper lymphocytes.
 

Hip

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This is what the study says:
Yes, the important sentence is:
immunostimulatory properties of ivermectin are associated with altered function of T lymphocytes, in particular, T-helper lymphocytes
If you look here, it says:
Helper T cells are arguably the most important cells in adaptive immunity, as they are required for almost all adaptive immune responses. They not only help activate B cells to secrete antibodies and macrophages to destroy ingested microbes, but they also help activate cytotoxic T cells to kill infected target cells.
So it looks like ivermectin increases antibody levels via its effect on helper T-cells.



So ivermectin might be useful for those with low antibody levels, and it's simulation of antibodies could explain why one study found it effective for COVID, because the newest research shows coronavirus may cause an autoimmune attack on antibody-producing B-cells.


Ivermectin's antibody stimulation is probably not going to help much for ME/CFS though, as ME/CFS patients tend to have intracellular infections which cannot be touched by antibodies. And in any case, ME/CFS patients tend to have very high antibody levels to their viruses anyway.

Although ME/CFS patients might benefit from some of the other effects of ivermectin immune stimulation.
 
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Learner1

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I had a plasmapheresis. 7 in 10 days. Did nothing. I took Rituximab did nothing. This is with a high probability not an autoimmune disease.
Did you have autoimmune antibodies causing symptoms? Did either the plasmapharesis it the Rituximab reduce the antibodies, which is how both treatments work?

Not everyone with ME/CFS has autoimmunity. There is a subset of patients who do, however. Treatments like plasmapharesis or Rituximab can help those patients.