Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 2023 Rohrhofer et al

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https://www.preprints.org/manuscript/202311.2007/v1

Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Johanna Rohrhofer
,
Lisa Hauser
,
Lisa Lettenmaier
,
Lena Lutz
,
Larissa Koidl
,
Salvatore Alessio Gentile
,
Davide Ret
,
Michael Stingl
,
Eva Untersmayr
*

Version 1 : Received: 30 November 2023 / Approved: 30 November 2023 / Online: 30 November 2023 (16:56:26 CET)

How to cite: Rohrhofer, J.; Hauser, L.; Lettenmaier, L.; Lutz, L.; Koidl, L.; Gentile, S.A.; Ret, D.; Stingl, M.; Untersmayr, E. Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Preprints 2023, 2023112007. https://doi.org/10.20944/preprints202311.2007.v1

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction.

Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients.

Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood.

This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients.

ME/CFS patients were stratified into two groups based on their immune competence.

After documentation of detailed medical records, serum and plasma samples were collected for assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA.

We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a sub-group specific innate immune dysregulation.

ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP).

Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns.

The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies.

Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.

 
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Not really clear how they are separating patients who they say do or don't have immunodeficiency:

The immunological stratification of the ME/CFS patients (Figure 1) was conducted during diagnostic evaluations prior to study participation. Before sampling of biological material, participants were asked to give a detailed medical record on background and individual symptoms. The information was collected to enable detailed stratification after the analyses of disease markers.

But even with this somewhat mysterious stratification, the differences they are showing do not look very significant:

upload_2023-12-4_20-21-12.png
Claiming there is a difference between groups here seems like a stretch:

upload_2023-12-4_20-22-12.png
Looks like there is something going on for some patients for (LBP) Lipopolysaccharide‐binding protein here, but definitely not all patients or all the ones they are calling non-immunodeficient:

upload_2023-12-4_20-24-39.png
 
"ME/CFS was diagnosed based on the Institute of Medicine (IOM) criteria [32] which define that following three symptoms and at least one of two additional manifestations are required for diagnosis. The three required symptoms are: (1) a substantial reduction/impairment in the ability to engage in pre‐illness levels of activity, (2) PEM and (3) unrefreshing sleep."
 
Looks like there is something going on for some patients for (LBP) Lipopolysaccharide‐binding protein here, but definitely not all patients or all the ones they are calling non-immunodeficient:

Interesting clustering there indeed! Makes me think about altered metabolism, as in a shift in equilibrium at some level. Looks like two different states, with the eternal caveat of ‘needs to be reproduced in a larger dataset’.
 
Up to 80,000 people in Austria are estimated to suffer from chronic fatigue syndrome, also known as ME/CFS or myalgic encephalomyelitis/chronic fatigue syndrome. The number of ME/CFS patients is expected to rise drastically due to long-term effects of the COVID-19 pandemic. However, research in the field has neither identified mechanisms of disease onset nor causal treatment approaches. Scientists at MedUni Vienna have now identified possible biomarkers that could improve the diagnosis and treatment of long-lasting and debilitating fatigue. The study has recently been published in the Journal of Clinical Medicine.

MedUni Vienna scientists identify possible biomarkers for chronic fatigue syndrome (msn.com)
 
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