MicroRNA Profiling of Blood Extracellular Vesicles in ME/CFS, 2025, Ljungström et al.

SNT Gatchaman

SNT Gatchaman

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MicroRNA Profiling of Blood Extracellular Vesicles in ME/CFS
Ljungström, María; Nathanson, Lubov; Oltra, Elisa

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating neuroimmune disease affecting many organs and systems which, in the absence of validated biomarkers, remains diagnosed by clinical criteria. Extracellular vesicles (EV) in blood come from practically all cells in our body and therefore may carry the disease-specific biomarkers needed for the diagnosis of ME.

This chapter presents the methodology used on a single pilot study performed to evaluate this possibility to describe a workflow for EV isolation and the analysis of the miRNAs within, which could serve to interrogate additional cohorts of ME/CFS. Among the diverse nature of EV contents miRNAs may constitute a prominent regulatory layer in the development and progress of complex diseases such as ME/CFS, and therefore their study should be further pursued.

Link | PDF (SpringerLink) [Paywall]
 
From the introduction —

MicroRNAs, also known as miRNAs or miRs are short non-coding RNAs, with a typical length of 20–24 nucleotides, and proven regulatory function of gene expression, mainly through mRNA degradation and translational repressing mechanisms. Findings of deranged miRNA levels in disease promptly captured the attention of many researchers for their potential as diagnostic biomarkers. Although ME/CFS was no exception, the potential biomarker of miRNAs in ME/CFS remains under-researched. This is illustrated by the fact that the number of publications pulled from PubMed using the keyword “miRNA” are over 165 k articles currently, while only 35 contain the keyword “Myalgic Encephalomyelitis”.
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The protective lipid bilayer of the vesicle constitutes a physical barrier from RNA-degrading enzymes, possibly leading to improved replicability of assays based on RNA quantitation.
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ISEV, the International Society for Extracellular Vesicles, endorses EV “as the generic term for particles naturally released from the cell that are delimited by a lipid bilayer and cannot replicate, i.e. do not contain a functional nucleus”. But the EV mix contains different types of vesicles: exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and other membranous structures, all presenting different diameters, lipid composition, and contents which also may vary in response to exogenous and endogenous stimuli as part of long-range communicating mechanisms.
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Thus, disease-associated EV may contain important “messages” holding biomarker value. Among the different potential messenger molecules found in circulating EV, miRNAs are of interest as they can regulate multiple gene targets, expanding their regulatory potential in target cells. A key advantage of miRNA-based diagnostic or prognostic methods is the high sensitivity that RT-qPCR-based methods provide by virtue of the obtained exponential amplification of template material which could permit early detection of the disease.
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Moreover, EV arrive to blood from all tissues, even from the nervous tissue, as EV can cross the BBB. Therefore, revealing EV contents may inform of processes occurring in the whole organism rather than in a particular cell type, an aspect of particular importance for the study of complex diseases, such as ME/CFS. The path to ME/CFS “liquid biopsy” may be packaged and “hidden” in patient blood EV, and yet the efforts invested in this direction seem minimal. To our knowledge, only one study among the over 2700 studies evaluating miRNA contents in blood-derived EV (current PubMed records) has explored those of blood circulating EV from ME/CFS.
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