Preprint [...] Plasmapheresis in [ME/CFS] Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies – a Pilot Study, 2025, Oesch-Régeni et al

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Effect on Quality of Life of Therapeutic Plasmapheresis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies – a Pilot Study

Boglárka Oesch-Régeni, Nicolas Germann, Georg Hafer, Dagmar Schmid, Norbert Arn

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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 β-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.

Link (Preprint: Preprints.org) [Open Access]
 
4.2. Data Collection and Patient Compliance
Working with ME/CFS patients can be challenging. The core symptom, the post-exertional ma- laise (the so-called "crushes") could interfere with the adequate data collection, even if the study group works with a well-established study protocol. Some of the patients suffered from recurring post-exertional malaise after the conduction of 6MWT. Therefore our study group decided to cease the 6MWT for the wellbeing of our patients. Consequently, the 6MWT dataset was not eligible for statistical analysis. ME/CFS itself, due to its main clinical manifestation characterized by exertion in- tolerance and the post-exertional malaise poses a huge challenge for adequate data collecting. Some- times during the crushes, ME/CFS patients have to cancel consultations or a blood test because of the major malaise. This can negatively impact the exact sample collection. One patient had to be excluded because of lacking baseline and follow-up clinical outcome data. 2 patients could be analyzed after data imputation.
They studied patients that crashed after participating in a 6 minute walk test…
4.3. Subjective Experience of Patients
Most patients reported a subjective benefit after the first PE + IVIG therapy, however it could be observed that many of them were crushed after the second round. This deterioration of the clinical status led to premature termination of the therapy in 3 cases. During the 4 treatments most patients experienced a gradual improvement in their symptoms. 5 of a total of 7 patients reported a subjective benefit after the PE therapy.
3/7 had to stop the treatment due to crashing, but at least one of them (and 5/7 in total) reported a subjective benefit.
 
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