Effect on Quality of Life of Therapeutic Plasmapheresis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated Ꞵ-Adrenergic and

[SWAlexander]

https://www.preprints.org/manuscript/202504.0228/v1

Abstract​

Background/Objectives: Recent studies brought evidence that the Long-Covid / post-COVID-19 Syndrome (PCS) and the related Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have an autoimmune pathomechanism[1]. It could be triggered by various infectious pathogens, like SARS-CoV-2, which may be one of the most common triggering factors of the disease. The identification of increased levels of autoantibodies alleged with the typical symptom-constellation of post-exertional malaise, sleeping disorders, cognitive malfunction, postural orthostatic tachycardia syndrome (POTS), etc. and several subjective health problems can lead to the correct diagnosis. ME/CFS patients have a high suffering level. Making a correct diagnosis is challenging, as well as the therapy of the complex and individual constellation of physical and psychical symptoms. Methods: Our aim was to identify the ME/CFS patients correctly, including an initial rule-in screening by investigating other possible causes (pulmonal/cardial/endocrine, etc.). In 7 cases we applied plasmapheresis (PE) with repetitive autoantibody-measurements. Additionally, according to references from literature, for monitoring the clinical outcomes psychometric follow-up assessments had been conducted: with the ISI (insomnia), FSS (fatigue), HADS (depression and anxiety) and EQ-5D-5L (quality of life) questionnaires. Patients who met the inclusion criteria received 4 PE sessions on day 1, 5, 30 and 60 and a low-dose intravenous immunoglobulin (IVIG) therapy after each treatment. The psychometric evaluation had been conducted before the first PE, 2 weeks after the second and two weeks after the last PE-therapy. All 4 antibodies were measured two times per patient over the course of the study at standardized sampling time points: baseline before starting PE and 2 weeks after the last PE. Results: It could be found a negative correlation between the ꞵ-Adrenergic and M3-muscarinic receptor antibodies concentration and the quality of life measurements assessed with the EQ-5D-5L questionnaire. Conclusions: In this pilot study a correlation could be shown between the autoantibody-concentration and the physical and psychical wellbeing of the treated ME/CFS patients. These first results should be seen as a hypothesis-building assessment, further investigation is needed to validate these promising pilot-study results of therapeutic PE and IVIG in ME/CFS cases.

 

[andyguitar]

Looks interesting @SWAlexander but the number of patients in the study is a bit to small to reach a conclusion.

 

[SWAlexander]

pilot-study results of therapeutic PE and IVIG in ME/CFS cases.

You're absolutely right, but every line of research has to start somewhere.
As noted at the end: “Further investigation is needed to validate these promising pilot-study results of therapeutic PE and IVIG in ME/CFS cases.” Hopefully, other researchers will take these initial findings as a springboard for deeper exploration.

 

[Wishful]

So, did severe patients go back to normal life, or did mild patients just answer questionnaires a few points higher, with no real change in their daily activity levels?

 

[SWAlexander]

So, did severe patients go back to normal life,

I'm confident that Preprints.org would be open to addressing your question. They aim to support scientific dialogue and often respond to inquiries like yours.

 

[kushami]

Thanks for posting this, @SWAlexander.

Looks like the study was done in Switzerland.

I think muscarinic receptor antibodies have come up in POTS research. Bit tired to look it up now, but it might have been Blair Grubb and colleagues. I know he was looking at antibodies a while ago.

Edit: Here is the paper I was thinking of. There are various types of muscarinic whatnots. Am still a bit tired and too lazy to see whether these studies are talking about the same ones.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6818019/

There are quite a few papers in the autonomic literature that mention beta adrenergic antibodies – too many for me to pick out the ones where it was detected as opposed to just being referenced.

I would now like to say something clever about autonomic dysfunction and how the study authors could have screened for that, and was the plasmapheresis treating CFS or autonomic dysfunction, or can we even separarate them. But I washed the dishes this evening and my legs are hurting

 

[cfs since 1998]

It's nice to see plasma exchange being looked at and published. I suspect this will have a similar success rate as IVIG and immunoadsorption. We need more, larger studies of all of these.

 

[Treeman]

The stumbling block I see is that we don’t know what’s in the blood and what’s been taking out.

I read there’s over 250 cytokines and over 80 autoantibodies known. None of the studies have this yet as a recorded outcome of what’s there and removed. And even if they are removed, do they come back?

I’m please to see this research but there still seems a long way to go.

 

[Sad Dad]

Anecdotally, IVIG did nothing for my daughter. However, she had plasmapheresis many times (3 / week for 3 months), and that is the only thing she's tried so far that has helped her. Plasmapheresis didn't get her anywhere near back to normal, but it did significantly improve her quality of life. Unfortunately, the benefits seem to have worn off after a year.

 

[Learner1]

Anecdotally, IVIG did nothing for my daughter. However, she had plasmapheresis many times (3 / week for 3 months), and that is the only thing she's tried so far that has helped her. Plasmapheresis didn't get her anywhere near back to normal, but it did significantly improve her quality of life. Unfortunately, the benefits seem to have worn off after a year.

Wouldn't that be because B cells just made more the bad antibodies? I've always looked at plasmapheresis as a test to see if a more permanent solution like Rituximab would work.

Rituximab was extremely helpful for me as it killed off the B cells making my bad antibodies and allowed a reboot to a more normal state after the B cells eventually grew back.

 

[cfs since 1998]

Anecdotally, IVIG did nothing for my daughter.

Sorry to hear that. What was the dose, frequency of infusion, and length of treatment? I believe the minimum to determine whether it works would be 4 months although it might need to be twice that long to make a difference.

However, she had plasmapheresis many times (3 / week for 3 months), and that is the only thing she's tried so far that has helped her. Plasmapheresis didn't get her anywhere near back to normal, but it did significantly improve her quality of life. Unfortunately, the benefits seem to have worn off after a year.

Well that's something! Maybe she will need continuous treatment?

 

[kushami]

The stumbling block I see is that we don’t know what’s in the blood and what’s been taking out.

I read there’s over 250 cytokines and over 80 autoantibodies known. None of the studies have this yet as a recorded outcome of what’s there and removed. And even if they are removed, do they come back?

I’m please to see this research but there still seems a long way to go.

The study says that they looked at four autoantibodies and found that, of those four, patients felt better when ꞵ-adrenergic and M3-muscarinic receptor antibodies were lower.

I assume that when the study is forrmally published, data tables will be included. Or maybe they will be added to the preprint. I think authors sometimes update it several times along the way. This reads like an abstract at this point.

 

[Sad Dad]

Wouldn't that be because B cells just made more the bad antibodies? I've always looked at plasmapheresis as a test to see if a more permanent solution like Rituximab would work.

Rituximab was extremely helpful for me as it killed off the B cells making my bad antibodies and allowed a reboot to a more normal state after the B cells eventually grew back.

That's an interesting perspective. We tried apheresis as a result of the micro-clot trials that were new about 2 years ago. As @Treeman said, the problem is that we don't know what was being filtered out of her blood that helped.