Role of pharmacological activity of autoantibodies in ME/CFS

[SWAlexander]

Abstract​

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a condition characterised by extreme fatigue, memory impairment, pain and other symptoms that vary from patient to patient. It affects about 0.9% of the population and is often triggered by an acute viral or bacterial infection, such as Epstein-Barr virus. The underlying physiological and molecular basis of ME/CFS is unknown, and no effective treatments exist.

One proposed mechanism is that the blood flow is altered by autoantibodies against receptors involved in blood flow regulation. Antibodies are generated by the immune system to recognise intruders and under normal conditions, our immune system is trained not to attack our own tissues. However, during a severe infection, the immune system adopts an "all hands on deck" approach, which results in some of the newly-produced antibodies escaping quality control and targeting our own tissues, autoantibodies. Receptors regulation blood flow are located in walls of blood vessels and cause a blood vessel to dilate or contract as the demand for oxygen and nutrients to tissues such as the brain or muscles changes. Research has found increased levels of these autoantibodies in ME/CFS patients and initial trials removing these autoantibodies from the blood using a technique called immunoadsorption have shown improvement in symptoms.
In this project, we will test the hypothesis that autoantibodies can activate or inhibit the receptors responsible for the blood flow regulation, in a similar way medical drugs are used to regulate blood pressure.
We aim to profile serum samples from 325 ME/CFS patients and 130 healthy individuals to determine the presence of autoantibodies against all thirty receptors involved in blood pressure regulation. Importantly, we will study the ability of autoantibodies detected in each sample to activate or inhibit these receptors in order to test the hypothesis that the activity of these autoantibodies is a decisive factor in the disease.

If our hypothesis is correct, we will be able to develop an accurate blood test that may be able to detect ME/CFS earlier or to independently confirm the diagnosis. Ultimately, we hope that these results may also indicate a possible route for therapeutic intervention to counteract the effects of autoantibodies and alleviate the ME/CFS symptoms using a combination of already existing drugs, specific for each individual case.
Continue reading: https://gtr.ukri.org/projects?ref=MR/Y003667/1&pn=0&fetchSize=25&selectedSortableField=date&selectedSortOrder=ASC&fbclid=IwAR0Qaoac3D4UF8XeNLiAh8NpvH2NkybCOn6HTMakq-nKO7h13a_qNvFqxvM

This is the key sentence: "However, during a severe infection, the immune system adopts an "all hands on deck" approach, which results in some of the newly-produced antibodies escaping quality control and targeting our own tissues, autoantibodies."

Finally, someone is looking beyond the obvious. Again and again, I suggested checking the Thymus function, hormones and Beta 2 Adrenergic Receptor.

Beta 2 Adrenergic Receptor PKA, PKC, PTK​

https://www.sciencedirect.com/topic...maceutical-science/beta-2-adrenergic-receptor

 

[Hoosierfans]

This is fantastic news. I have GPCR antibodies all over the place and, as one member here said, in Europe GPCR antibodies are the second coming of Jesus…in the US doctors don’t give a ____! And that’s been my experience.

 

[datadragon]

When I looked into autoantibodies, I was surprised that butyrate was a main player and this also happens to be a downstream effect (low butyrate) of the lowered zinc availability during inflammation/infection states. Later the NIH had confirmed the low butyrate with me/cfs in the second link (as opposed to just general research).

Short chain fatty acids including butyrate exert modulatory effects on intrinsic B cell functions even at moderate concentrations, thereby is what shapes normal and effective antibody and autoantibody responses. So that means that when butyrate is low it can cause the dysregulated antibody responses leading to generation of autoantibodies. https://forums.phoenixrising.me/threads/bc007-what-are-your-thoughts.87520/post-2441668 and https://forums.phoenixrising.me/thr...s-chronic-fatigue-syndrome.90582/post-2446324

 

[junkcrap50]

Nice large study. 325 ME/CFS patients, 130 healthy, 455 total patients! Hopefully some good results will come out.

Except unfortunately, not all ME/CFS patients have autoantibodies and those that do don't have the same ones. So hopefully the study size is large enough.

What's the date of this announcement and expected study start date? It says funded period is October 23 - March 25. Does that mean it's already funded? Or it is currently in fundraising mode?

 

[SWAlexander]

Does that mean it's already funded?

Maybe, since the last line is: "Ultimately, our findings may point in the direction of developing combination therapy using repurposed drugs to counteract the effects of autoantibodies and mitigate ME/CFS symptoms and stimulate the development of specific B-cell elimination strategy to cure ME/CFS."

 

[Hoosierfans]

I emailed the principal investigator and he responded very kindly:

Dear Tiffany,
many thanks for your email and for your encouraging words! Much appreciated.
We are basic researchers coming from a molecular pharmacology
background. In this pilot study, we will use already collected plasma
samples from the UK ME/CFS biobank
(https://cureme.lshtm.ac.uk/the-uk-mecfs-biobank/). If we are
successful and our hypothesis will be proven (in ca 12-18 months), we
will apply for a followup grant to extend this study and to work
closely with clinicians and patients. Meanwhile, we are planning to
have several webinars hosted by the ME Association
(https://meassociation.org.uk/) about the progress of the project, but
dont have the dates yet.
Best regards, Dmitry

 

[nystew]

https://www.psychiatrist.com/news/a-novel-blood-test-could-revolutionize-chronic-fatigue-diagnosis/#:~:text=A novel blood test based,reliance on self-reported diagnosis.

Test came out September 2023

 

[Hoosierfans]

Test came out September 2023

That test isn’t commercially available yet. Indeed, it needs validation through larger studies before it becomes commercially available: “They said that they need further validation in much larger cohorts before any tests can be widely implemented.”

 

[Hoosierfans]

After further discussion via email with the researchers, I have high hopes for this study.

My immunologist explained to me that high levels of GPCR antibodies doesn’t really tell us much. It tells us that I have something autoimmune going on, but doesn’t tell us how these antibodies are FUNCTIONING….are they upregulating a receptor or downregulating it? So, for example, if you have an antibody to Antiogensin receptors you could have problems with vasodialator OR vasoconstriction, or both! Obviously that’s problematic when you are trying to treat — do you give that patient midodrine to increase their blood pressure and vasoconstriction or beta blockers to help increase vasodialation and lower their blood pressure. Or do you need to give them both??

We simply don’t know. Dmitry, the principle investigator, confirmed this and explained that that is why they are looking at the FUNCTIONALITY of these antibodies. Not just if they are present or not.

So it will help to answer two questions — whether these antibodies have any pathology in ME / CFS (which most docs in the US think they do NOT); and what the pathology actually IS. 👍🏻👍🏻👍🏻👍🏻