You probably have an autoimmune disease...

[sometexan84]

If a disease is caused or contributed to by autoantibodies, then it should improve via plasmapheresis, which is where a patient's blood plasma (in which antibodies float) is removed, and replaced with pure saline.

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.

 

[sometexan84]

I developed ME in 2008 followed by systemic lupus erythematosis in 2014. My lupus is very well controlled with methotrexate and plaquenil and yet this has not improved the severity, frequency and duration of ME fatigue, cognitive problems. If it was really autoimmune then the fatigue should improve along with the SLE symptoms. It doesn't.

Well yea, I mean I was diagnosed w/ Hashimoto's thyroiditis before I even heard about CFS. Treating this and returning my thyroid levels to normal had no improvement on my symptoms either.

Then I was diagnosed w/ Obstructive Sleep Apnea, again before I'd heard of CFS. Using a CPAP machine didn't improve my symptoms either. (btw, I believe my sleep issues are autoimmune related as well)

You probably have other auto-antibodies and other autoimmune conditions (e.g. Crohn's disease, Antiphospholipid Syndrome).

• Systemic lupus erythematosus (SLE) – Usually has high IL-10, ANA is almost always positive
  • SSA 52 kD (Ro52) IgG antibodies; dsDNA IgG in 60% SLE
  • Anti-U1A autoantibodies (P = 0.01), U1A might not be the same as U1
  • mitochondrial RNA (AmtRNA)
  • Phosphatidylserine/Prothrombin ab in 31% SLE
  • Saccharomyces cerevisiae antibodies found in 32%
  • DR8 (DRB1*08:01) association
  • Infections: EBV, Toxoplasma gondii

Also, NMDA (N-methyl-D-Aspartate Receptor) antibodies have been found in SLE.

And SLE can cause Glomerulonephritis (GN), as well as Transverse Myelitis (inflammation of the spinal cord)

 

[borko2100]

It is quite possible that an auto-immune subset does exist. However I find it difficult to explain PEM and energy issues with autoimmunity alone.

 

[Hip]

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

Plasmapheresis would be a good way to determine if ME/CFS had major type II autoimmune components: just place a large group of ME/CFS patients on a course of daily plasmapheresis for say two weeks, and see if they got better.

The study you linked to already provides some evidence, but that only selectively removed certain autoantibodies with immunoadsorption, which is an antibody-specific form of plasmapheresis.

But plasmapheresis most likely will not offer any lasting benefits.

However I find it difficult to explain PEM and energy issues with autoimmunity alone.

A German group found enterovirus infection could induce autoantibodies which target the ANT protein on mitochondria, whose function is to transport ATP out of the mitochondria for use in the cell, and transport the spent ATP back into the mitochondria for recycling. See this thread.

 

[gbells]

It is quite possible that an auto-immune subset does exist. However I find it difficult to explain PEM and energy issues with autoimmunity alone.

I think Prusty's research on mitochondrial fragmentation due to HHV6 and other viruses is much more compelling than this autoimmunity hypothesis. You guys should watch the video. He took virus free cells serum and found a chemical from the viruses that is causing the fragmentation in healthy cells which inhibited their mitochondria. Think about it, if multiple viruses each cause fragmentation, contribute to apoptosis inhibition and turn the cell into a drug factory for a mitochondrial inhibitor then combined their effect would be devastating. This supports my viral coinfection theory of ME.

 

[Alvin2]

Plasmapheresis would be a good way to determine if ME/CFS had major type II autoimmune components: just place a large group of ME/CFS patients on a course of daily plasmapheresis for say two weeks, and see if they got better.

If this were checked as a study and produced positive results it would be an amazing breakthrough, because it would be excellent evidence that ME is based on something filtered out, and would provide a concrete direction. It could even be used to lobby governments for funding because unlike the CBT BS this would be reproducible and would lead to many targeted research grant proposals.

 

[Hip]

If this were checked as a study and produced positive results it would be an amazing breakthrough, because it would be excellent evidence that ME is based on something filtered out, and would proved a concrete direction. It could even be used to lobby governments for funding because unlike the CBT BS this would be reproducible and would lead to many targeted research grant proposals.

The downside is that rituximab did not improve ME/CFS in Fluge and Mella's phase III clinical trial. Rituximab kills all the B-cells in the blood which make antibodies. So you might expect that if ME/CFS was autoimmune, rituximab would have fixed it. Everybody was hoping for that.

However, it's not quite that simple, as rituximab does not kill the antibody‐producing plasma cells in the blood.

I think Prusty's research on mitochondrial fragmentation due to HHV6 and other viruses is much more compelling than this autoimmunity hypothesis. You guys should watch the video. He took virus free cells serum and found a chemical from the viruses that is causing the fragmentation in healthy cells which inhibited their mitochondria.

Prusty's research is interesting. Other researchers have found similar things regarding "something in the serum" affecting cell energy production — see this thread. The blood serum is where you find antibodies and immune signaling molecules.

 

[sometexan84]

However I find it difficult to explain PEM and energy issues with autoimmunity alone.

I'm sure you do. If you've done your research, then you know that what I'm saying isn't something that gets much attention.

Can you explain PEM period? Because researchers still can't.

Like I said above, "That's because other conditions don't use "PEM", they say "exercise intolerance". PEM is mostly a name used in CFS. While "exercise intolerance" is a little more ambiguous and vague, it can for sure mean the same thing."

No one has PEM, looks up that symptom, then thinks "Oh, so I guess I have CFS".

People only hear the term "PEM" after they've learned about CFS. And then they're like oh, so "Post Exertional Malaise"...... "yea, I have that."

Like Cort said, not too long ago... It was ME/CFS experts, after all, not POTS or fibromyalgia specialists, who coined the term post-exertional malaise (PEM) decades ago
https://www.healthrising.org/blog/2...tigue-syndrome-and-hyperadrenergic-pots-meet/

There are definitely others out there that have PEM. Except, they have never heard of PEM, or CFS. And the doctor they see doesn't know about those two things either. But they'll probably discover an autoimmune disorder.

Going back to Small Fiber Polyneuropathy ....

Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review
Immunohistopathologic evidence suggests that small-fiber dysfunction and denervation, especially of blood vessels, contributes to diverse symptoms, including postexertional malaise, postural orthostatic tachycardia, and functional gastrointestinal distress

Sound familiar? This is an autoimmune disease w/ multiple auto-antibodies involved.

Antiphospholipid Syndrome shows the same type of impaired aerobic capacity, with blood vessel clotting issues and damage to autonomic nervous system fibers.
Sticky Blood” – Antiphospholipid Syndrome, POTS, Chronic Fatigue Syndrome and Fibromyalgia – The Dysautonomia Conference #4

And sure enough....

Phospholipid autoantibodies in ME/CFS patients and antibodies against cardiolipin were described in 92–95% of ME/CFS patients in two studies.
https://www.sciencedirect.com/science/article/pii/S1568997218300880

There's also "PEM" in heart preload failure - https://endmecfs.mgh.harvard.edu/heartpreload/

There's the PEM in cancer I'd linked to earlier. It's seen in POTS. And probably a lot of other conditions.

All this stuff has common denominators - bloodflow, blood pressure, blood volume, autonomic dysfunction, abnormal sympathetic activation, and for sure autoimmunity and fatigue.

A good 2019 article I recommend - Fatigue, Sleep, and Autoimmune and Related Disorders

a growing literature indicates that fatigue is common in most autoimmune-related diseases, as well as among individuals with related immunodeficiency disorders

98% of individuals with autoimmune disease report that they suffer from fatigue

 

[sometexan84]

A German group found enterovirus infection could induce autoantibodies which target the ANT protein on mitochondria, whose function is to transport ATP out of the mitochondria for use in the cell, and transport the spent ATP back into the mitochondria for recycling. See this thread.

This is one possibility of many.

Coxsackie 3 alone induces the following (these are just the ones I found so far....)

• Coxsackie 3: Myosin
• Coxsackie 3: Adenine nucleotide translocator (ANT) antibodies
• Coxsackie 3: Anti-flavoprotein antibodies
• Coxsackie 3: Actin (Anti-smooth muscle antibody)
• Coxsackie 3: Tropomyosin (Anti-smooth muscle antibody)
• Coxsackie 3: Heat shock proteins
• Coxsackie 3: Desmin
• Beta-cell autoantibodies (aka islet cell)

ANT, yes that can cause major energy issues.

Myosin, tropomyosin, desmin, these are all antibodies that can effect your heart, blood pressure and blood flow. They can be very serious.

Actin can be seen in Autoimmune Hepatitis, which has all sorts of complications surrounding it. This is liver inflammation, and fatigue is a major symptom.

And this is all just Coxsackie 3 auto-antibodies... which is nothing compared the the autoantibodies that EBV and Parvovirus B19 can induce.

 

[Alvin2]

The downside is that rituximab did not improve ME/CFS in Fluge and Mella's phase III clinical trial. Rituximab kills all the B-cells in the blood which make antibodies. So you might expect that if ME/CFS was autoimmune, rituximab would have fixed it. Everybody was hoping for that.

However, it's not quite that simple, as rituximab does not kill the antibody‐producing plasma cells in the blood.

I see.
I have to admit that my knowledge of immunology is not great.

That said if this worked and was published in a reputable journal and was repeatable it would jump start interest in ME/CFS.

 

[sometexan84]

I think Prusty's research on mitochondrial fragmentation due to HHV6 and other viruses is much more compelling than this autoimmunity hypothesis

You know, there are auto-antibodies that have been found that help induce mitochondrial fragmentation (fission).

 

[sometexan84]

If this were checked as a study and produced positive results it would be an amazing breakthrough, because it would be excellent evidence that ME is based on something filtered out, and would provide a concrete direction. It could even be used to lobby governments for funding because unlike the CBT BS this would be reproducible and would lead to many targeted research grant proposals.

This would be a good study.

 

[sometexan84]

The downside is that rituximab did not improve ME/CFS in Fluge and Mella's phase III clinical trial. Rituximab kills all the B-cells in the blood which make antibodies. So you might expect that if ME/CFS was autoimmune, rituximab would have fixed it. Everybody was hoping for that.

However, it's not quite that simple, as rituximab does not kill the antibody‐producing plasma cells in the blood.

I still think there's a treatment role for rituximab. But it has to be precise, done at the right time.

Rituximab also does not destroy the auto-antibodies causing symptoms. Or the infections that will just create more auto-reactive B-cells later on. (EBV)

And science (at least to my knowledge) has not yet determined how long auto-antibodies stick around. Who's to say some don't stick around indefinitely, continuously attacking an organ w/out intervention?

I mean, I tested for High anti-phosphatidylserine antibodies. I can only find Parvovirus B19 that produces this. At my B19 IgG levels, it's likely I had this acute infection back in like 2016. Yet, these antibodies are still in my system.

 

[pattismith]

@sometexan84

I still don't know if my ME/CFS/fibro is auto-immune or not, and I don't think we have definite proof it's an autoimmune disease.

Grave's thyroiditis is an evident auto-immune disease; it is tightly associated with a single Ab type (anti TSH receptors) and resolves when these Ab are cleared.

The fact anti-muscarinic and anti-adrenergic Ab are associated with ME/CFS is not a proof ME/CFS is a primary auto-immune disease. These Ab are not specific, they happen in many auto-immune and neuro-degenerative diseases.

However, post-viral sudden onset ME/CFS with POTS have more chance to be a primary auto-immune disease...
or sudden ME/CFS + associated sudden Small fiber Neuropathy for example.
And some diseases are suspected auto-immune without any specific auto-antibody found,
like Narcolepsy type 1, which has some auto-immune features. it is tightly associated with a HLA type and is believed to depend on T Lymphocytes CD8 auto-immune activity.

In order to study auto-immunity in ME/CFS and Fibro, you need more specific criteria and biological markers.

 

[gbells]

Phospholipid autoantibodies in ME/CFS patients and antibodies against cardiolipin were described in 92–95% of ME/CFS patients in two studies.

I wouldn't be surprised in the least of this because the cells are infected so the viral infections are the stimulus behind the autoantibodies. Of course the body wants to kill them off. But just like drug induced lupus where the stimulus is the drug, remove the source of the stimulus and the antibodies go away via a feedback loop.

Can you explain PEM period? Because researchers still can't.

Sure, post exercise malaise is when cell growth is blocked. Mitochondral fragmentation means that infected mitochondria can't reproduce. The reason why ME patients can't respond to strength training normally is that the body has blocked recovery in order to hamper the spread of the viruses. This means that the amount of recovery is limited. What is fascinating is that it only affects the mitochondria and not the growth of the rest of the cell. This gives us hope that the viruses wouldn't spread to all of the body cells and that the ME could be treatable through enhancing apoptosis.

So rather than seeing ME fatigue as the enemy perhaps it should be seen as an important disease slowing defense.

You know, there are auto-antibodies that have been found that help induce mitochondrial fragmentation (fission).

Prusty is a proponent of drugs to eliminate mitochondral fragmentation as a cure for ME but I am pessimistic about this treatment. If the body wants to slow the spread of the body and you stop it's protective response then you end up with more infected cells and worsening problems. It would end up masking the symptoms while the patient gets worse. These cells are cancer and heart disease factories and create depression. If the fatigue is slowing a person's decline then the last thing you want to do is to stop it.

 

[Hip]

@Hip do you know of any items that maybe of use against hypogammaglobulinemia?

Here is one study which found that in mice, ivermectin stimulates the production of antibodies, via a mechanism involving T-cells.

 

[gbells]

Here is one study which found that in mice, ivermectin stimulates the production of antibodies, via a mechanism involving T-cells.

And the antibodies would be blocked from attachment to the cell membrane by the EBV blocked FasL receptor. So that goes nowhere.

 

[Hip]

And the antibodies would be blocked from attachment to the cell membrane by the EBV blocked FasL receptor. So that goes nowhere.

I am not sure what you are referring to.

@Treeman asked me above if I knew anything which could stimulate antibody production, as he has hypogammaglobulinemia, which results in low levels of antibodies and immune weakness.

 

[crypt0cu1t]

This would be great if it led to research direction.
If someone experienced improvement on this it would suggest where we need to look for the cause of this disease.

Has anyone tried it?

I did 7 rounds of plasmapheresis and noticed a decent improvement about a week later.

 

[Canned]

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.