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NICEGUIDELINEBLOG = study points 95% PWCs have autoimmune disease

Sasha

Fine, thank you
Messages
17,863
Location
UK
Thanks for posting - yes, weird this is a 2009 study and we've never heard of it.
 

fla

Senior Member
Messages
234
Location
Montreal, Canada
I joined the National CFIDS Foundation almost a year ago because they were the only ones investigating the auto-immunity link in M.E. When I joined they mentioned a test at the University of Hawaii but I declined to take it since it would also be positive if you have other auto-immune diseases also and I do but if M.E. is your only disease you might consider it.
 

Nielk

Senior Member
Messages
6,970
Specifically, Rituximab, a chimeric monoclonal CD20 antibody, has been shown to normalize high ACA serum titers of patients with autoimmune systemic lupus erythematosus, rheumatoid arthritis, autoimmune thrombocytopenia, and autoimmune hemolytic anemia. Rituximab may serve as an effective therapeutic agent for ameliorating the symptoms of CFS (11,13).

Therefore, classification of CFS as an autoimmune disorder may serve to increase the availability of treatment options for patients suffering from the disease.

This was published in 2009!
 
Messages
180
Has anyone thought about how the autoimmune aspect might be reconciled with the gene expression alterations detected by Light et al?

?-2A Increase Subgroup (34/48 CFS subjects): This group exhibited
large gene expression increases after exercise in the following genes:
P2X4, P2X5, TRPV1, ?-2A, ?-1, ?-2, COMT and IL10. "Interestingly, the
genes found to be dysregulated in the present study represent most of
the pathways hypothesized by others to be altered in CFS.

At first glance I can't see an obvious way that the two could fit together, ACA autoantibodies attacking mitochondria can explain a portion of the symptomatology but not all, and I struggle to see how pain/fatigue receptors would be upgregulated as a result of these autoantibodies. That said, my knowledge of autoimmune diseases is very limited so I'd love it if someone could enlighten me.
 

fla

Senior Member
Messages
234
Location
Montreal, Canada
My guess would be that in a subgroup the autoimmunity is causing extreme oxidative stress which ends up depleting glutathione which then causes excessive gene expression.
 

kurt

Senior Member
Messages
1,186
Location
USA
Wow, I just told someone earlier today that if we have an autoimmune condition it must be attacking the mitochondria. Holy cow, that's probably exactly what is happening! The triangulation now with the Mella and Fluge study should really push this 2009 study into the mainstream of ME/CFS research.

So basically, if I am interpreting this correctly, any time our B cells become activated, such as a re-exposure of a viral insult for which we already have antibody memory, then our mitochondria will be attacked by autoantibodies? If EBV is somehow staying semi-active, then it stands to reason that anything that aggravates the EBV (stress is known to do that, or modulation of immune function) would then set of a cascade of events, since there is plenty of antibody memory of EBV right in the B cells! Wow, that could really make the ME/CFS model simple, Occam would approve...

Regarding the Lights' studies, IF the pain receptors are down-stream of a mitochondria insult (I believe there is research showing that to be true), then attacking the mitochondria might lead to some type of release of signals from the mitochondria to the pain/fatigue receptors. Just speculating, but I don't think it will be difficult at all to connect those two factors (pain/fatigue receptors and mitochondria).

see: http://www.jneurosci.org/content/31/36/12982.abstract
 
Messages
16
Ok its sent :)

Doesnt this point to what Ken Lassesen has been saying all alone. The microthrombosis theory. Chronic low level hypercoagulation in this disorder. This would be an effect of the anti cardiolipin antibodies and could
in turn produce many of the cfs symptoms, hypoperfusion, memory problems, autonomic issues, maybe also gut, liver and kidney issues.

"Antiphospholipid syndrome

Patients with anti-cardiolipin antibodies (Antiphospholipid syndrome) can have recurrent thrombotic events even early in their mid- to late-teen years. These events can occur in vessels in which thrombosis may be relatively uncommon, such as the hepatic or renal veins. These antibodies are usually picked up in young women with recurrent spontaneous abortions. In anti-cardiolipin-mediated autoimmune disease, there is a dependency on the apolipoprotein H for recognition.[29]"

I know a patient story with the same distinct improvement as in the norwegian study, however it was an immediate response.
A swedish guy got clopidogrel for some heart issue and as soon as he took it his CFS symptoms disappeared.
He took it until his doctor didnt allow it anymore and he returned with to the same cfs state.
 
Messages
180
Another thing I just realised, if this is indeed getting close to the central pathological mechanism of the illness, then Low Dose Naltrexone surely becomes a must-try treatment for anyone that believes they may fit within that subgroup:

Endorphins effect the immune system by enhancing natural killer cell response and reducing B-cell (antibody) activity and LDN's effectiveness is being tested in several autoimmune diseases.

LDN appears to effect the functioning of the regulatory immune cells in the central nervous system called microglial cells. Upon activation by infection or cell damage micoglial cells produce pro-inflammatory cytokines, reactive oxygen species (free radicals) and nitric oxide. Microglial cells may be a key component of the 'sickness response' that produces fatigue, fluey feelings, pain, etc. when we come down with an infection. Some researchers believe that microglial cells are chronically turned on in ME/CFS and fibromyalgia. LDN appears to block a receptor on the microglial cells thus inhibiting their activation.

LDN might be having the same effects as Rituximab but obviously in a less drastic way.
 

FunkOdyssey

Senior Member
Messages
144
Autoimmunity. 1995;21(3):161-71.
Beta-endorphin and the immune system--possible role in autoimmune diseases.
Mrch H, Pedersen BK.
Source

Department of Rheumatology, Hvidovre Hospital, Copenhagen, Denmark.
Abstract

The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative feed back on the antibody production and potentially so on the production of autoantibodies.

PMID: 8822274

In one of the multiple sclerosis studies that tracked beta-endorphin levels, LDN raised beta-endorphin ~100% over baseline IIRC.

In another study that looked at 3 month and 6 month time points, beta-endorphin levels were STILL rising SIX months after initiation of therapy. It kills me every time I read someone tried LDN for a few weeks and dropped it because they didn't think it was doing anything. This a marathon, not a sprint.
 

FunkOdyssey

Senior Member
Messages
144
In addition to beta-endorphin, opioid growth factor is another endogenous opiate whose production is upregulated by LDN, arguably more important than beta-endorphin (especially if you ask Ian Zagon):

Immunobiology. 2011 Jan-Feb;216(1-2):173-83. Epub 2010 Jun 11.
B lymphocyte proliferation is suppressed by the opioid growth factor-opioid growth factor receptor axis: Implication for the treatment of autoimmune diseases.
Zagon IS, Donahue RN, Bonneau RH, McLaughlin PJ.
Source

Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USA. isz1@psu.edu
Abstract

Endogenous opioids are known to repress the incidence and progression of autoimmune diseases. One native opioid peptide, [Met?]-enkephalin, termed the opioid gowth factor (OGF), interacts with the OGF receptor (OGFr) to suppress the expression of experimental autoimmune encephalomyelitis. The present study examined the role of the OGF-OGFr axis in the regulation of B lymphocyte proliferation. Murine B lymphocytes were stimulated with lipopolysaccharide. Both OGF and OGFr were present in all B lymphocytes. OGF had a dose-dependent effect on growth, with cell number inhibited by up to 43% at 72 h; no other synthetic or native opioid altered cell proliferation. Exogenous OGF depressed cell number in cultures treated with siRNAs for the classical opioid receptors, MOR (?), DOR (?), and KOR (?), however this peptide had no effect in preparations exposed to siRNA for OGFr. The decrease in cell number by exogenous OGF was dependent on p16 or p21 cyclin-dependent inhibitory kinase pathways. Exposure to the opioid antagonist, naltrexone, did not change cell number from control levels. These results suggest that the OGF-OGFr axis is present and functional in B lymphocytes, but this system is not an autocrine regulator of cell proliferation. Thus, at least exogenous OGF and perhaps endogenous OGF by paracrine/endocrine sources, can be an immunosuppressant. Modulation of the OGF-OGFr axis may be a novel paradigm for the treatment of autoimmune diseases.

Copyright 2010 Elsevier GmbH. All rights reserved.

PMID: 20598772
 
Messages
180
In one of the multiple sclerosis studies that tracked beta-endorphin levels, LDN raised beta-endorphin ~100% over baseline IIRC.

In another study that looked at 3 month and 6 month time points, beta-endorphin levels were STILL rising SIX months after initiation of therapy. It kills me every time I read someone tried LDN for a few weeks and dropped it because they didn't think it was doing anything. This a marathon, not a sprint.

Interesting, thanks for that. I'm fairly sure I'm going to start this treatment as soon as possible, as long as my test results support the hypothesis. I'm guessing cytokine profiles, NK cell function and presence of TH1-TH2 shift are going to be the best indicators?
 

Waverunner

Senior Member
Messages
1,079
Another thing I just realised, if this is indeed getting close to the central pathological mechanism of the illness, then Low Dose Naltrexone surely becomes a must-try treatment for anyone that believes they may fit within that subgroup:
LDN might be having the same effects as Rituximab but obviously in a less drastic way.

Thanks for your input, Vitalic. I didn't know that LDN decereases B-cell activity.