Extracellular Vesicle Protein and MiRNA Signatures as Biomarkers for Post-Infectious ME/CFS Patients, 2026, Seifert et al

[forestglip]

Extracellular Vesicle Protein and MiRNA Signatures as Biomarkers for Post-Infectious ME/CFS Patients

Spoiler: Authors

Seifert, Martina; Schäfers, Johannes; Douglas, Fiona F.; Schwarzburg, Carl; Boristowski, Diana; Birke, Anne; Klein, Oliver; Sotzny, Franziska; Rubarth, Kerstin; Windzio, Lara; Beez, Christien M.; Peters, Claudia Kedor; Wittke, Kirsten; Scheibenbogen, Carmen; Greco, Anna

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Abstract
Post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with unresolved pathophysiology and limited diagnostic options. Extracellular vesicles (EVs) carry disease-specific protein and miRNA signatures and may enable improved disease profiling.

We aimed to identify novel protein and miRNA markers as potential biomarkers in plasma EVs from female ME/CFS patients, including post-COVID-19 ME/CFS and post-infectious ME/CFS of other origins, compared with healthy controls. EVs were isolated from plasma by size-exclusion chromatography and characterized for number, size, morphology, and surface marker expression.

Flow cytometry showed that small EVs strongly expressed tetraspanins, with only minor differences between ME/CFS patients and healthy donors. Proteomic profiling of EVs from ME/CFS patients identified altered cargo proteins, including hemoglobin subunit alpha and insulin-like growth factor-binding protein acid labile subunit compared with healthy controls (n ≤ 10/cohort).

Small RNA sequencing followed by qPCR revealed significant downregulation of hsa-let-7b-5p in EVs from post-COVID-19 ME/CFS patients (n = 12) versus healthy controls (n = 15). Reduced hsa-let-7b-5p expression correlated with impaired physical functioning and increased fatigue, pain, and immune activation.

These findings indicate that EV cargo differences, particularly hemoglobin subunit alpha and insulin-like growth factor-binding protein acid labile subunit, as well as hsa-let-7b-5p, represent promising candidates for ME/CFS diagnosis and patient stratification.

Web | DOI | PDF | International Journal of Molecular Sciences | Open Access

 

[Simon M]

I would love to see researchers come together to agree standards for ME/CFS biomarker research. This might include minimum sample sizes, including a validation cohort, at least one disease control group and being clear on the degree of biomarker overlap between patients and others.

We've seen a steady flow of these papers this century, and I'm not aware of any progress in either identifying clinically useful biomarkers or greater understanding of the underlying pathology.

 

[V.R.T.]

I would love to see researchers come together to agree standards for ME/CFS biomarker research. This might include minimum sample sizes, including a validation cohort, at least one disease control group and being clear on the degree of biomarker overlap between patients and others

This sounds like something PRIME could maybe do?

 

[Utsikt]

It seems like they are comparing post-covid HC to post-covid ME/CFS, and precovid HC to precovid post-infection ME/CFS.

2.1. Study Design
Plasma samples were collected from three study groups: post-COVID-19 ME/CFS (pcME/CFS) patients, post-infectious ME/CFS (piME/CFS) patients and the corresponding healthy controls with self-reported SARS-CoV2 infection (pcHC) and pre-pandemic healthy donors (HC), respectively (see Figure 1).

The female patient and control groups in the validation cohorts for protein markers (Table 1) and miRNA markers (Table 2) were similar in their age and body mass index. The piME/CFS group was younger and had a longer disease duration (median 24.45 months vs. 10 months in pcME/CFS). For the HCs, the self-reported time since the last SARS- CoV-2 infection was approximately 10 months. Both patients study groups showed similar disease and symptom severity (Table 1).

Does that mean that the ME/CFS specific signals might be the ones that overlap for both ME/CFS groups?

 

[DMissa]

I would love to see researchers come together to agree standards for ME/CFS biomarker research. This might include minimum sample sizes, including a validation cohort, at least one disease control group and being clear on the degree of biomarker overlap between patients and others.

The problem is that this will never be feasible because of money (even if everybody somehow agreed to a standard which I don't see happening). Different experiments etc will cost differing amounts to do and what might be possible to afford 100 people from the typical philanthropic grants we survive off of might be enough for 10 samples in something else

We've seen a steady flow of these papers this century, and I'm not aware of any progress in either identifying clinically useful biomarkers or greater understanding of the underlying pathology.

My guess is that the right things have not been zoomed in on yet. If somebody thought of the right thing that ended up being a key mediator of symptoms I expect you'd see a promising signal even in a smaller cohort