High-Throughput Sequencing of Plasma MicroRNA in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Brenu, Ekua; Ashton, Kevin J.; Batovska, Jana; Staines, Donald; Marshall‐Gradisnik, Sonya

doi:10.1371/journal.pone.0102783

Cited by 39 publications

(64 citation statements)

References 70 publications

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“…Researchers and clinicians seem to agree on the urgent need for unbiased, specific diagnostic biomarkers for ME/ CFS to expedite patient diagnosis and treatment, and to abolish disease stigmas for good 45 . There is also a consensus on the advantages that miRNA profiles from different blood fractions, EVs included, exhibit as molecular diagnostic candidates, and yet, a paucity of studies focusing on ME/CFS miRNA profiling is detected 22,[24][25][26][27] .…”

Section: Discussionmentioning

confidence: 99%

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Almenar-Pérez

Sarría

Nathanson

et al. 2020

Sci Rep

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Myalgic encephalomyelitis/chronic fatigue Syndrome (Me/cfS) is a debilitating multisystemic disease of unknown etiology, affecting thousands of individuals worldwide. Its diagnosis still relies on ruling out medical problems leading to unexplained fatigue due to a complete lack of disease-specific biomarkers. Our group and others have explored the potential value of microRNA profiles (miRNomes) as diagnostic tools for this disease. However, heterogeneity of participants, low numbers, the variety of samples assayed, and other pre-analytical variables, have hampered the identification of diseaseassociated miRNomes. In this study, our team has evaluated, for the first time, ME/CFS miRNomes in peripheral blood mononuclear cells (pBMcs) and extracellular vesicles (eVs) from severely ill patients recruited at the monographic UK Me biobank to assess, using standard operating procedures (Sops), blood fractions with optimal diagnostic power for a rapid translation of a miR-based diagnostic method into the clinic. Our results show that routine creatine kinase (CK) blood values, plasma EVs physical characteristics (including counts, size and zeta-potential), and a limited number of differentially expressed PBMC and EV miRNAs appear significantly associated with severe ME/CFS (p < 0.05). Gene enrichment analysis points to epigenetic and neuroimmune dysregulated pathways, in agreement with previous reports. Population validation by a cost-effective approach limited to these few potentially discriminating variables is granted.Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease characterized by long-lasting (over 6 months) persistent debilitating widespread fatigue, which is exacerbated by exercise (post-exertional malaise or PEM), and not alleviated by rest 1-5 . It has been classified by the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) with code R53.82 or G93.3 if post-viral 6 . It affects at least 0.23 to 0.41% of the population worldwide 7,8 , although numbers can reach up to 5% depending on the diagnostic criteria and geographic locations, according to a recent revision by the EUROpean Myalgic Encephalomyelitis Network (EUROMENE) epidemiology working group 9 . The disease strikes people of all ages and within all socio-economic levels, being more common in women (female:male ratios between 2:1 and 6:1) 7-10 . ME/CFS is considered a life-long disabling disease, since only about 5% of patients return to their previous state of health 11 .The confusion among General Health Practitioners (GPs) due to multiple clinical definitions 12 and the large number of comorbidities, such as fibromyalgia, IBS (irritable bowel syndrome), POTS (postural orthostatic tachycardia syndrome), depression, etc, stigmatized the disease, delaying diagnosis and treatment of patients. This highlights the urgent need of unbiased, specific methods to diagnose ME/CFS in a clinical setting.

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Section: Discussionmentioning

confidence: 99%

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Almenar-Pérez

Sarría

Nathanson

et al. 2020

Sci Rep

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“…Although, miRNAs such as miR‐150 and miR‐143 were reported in older patients with CFS, especially higher expression and sequencing of plasma miRNAs in patients with CFS/myalgic encephalomyelitis, it is not known whether the proposed miRNAs are expressed or have a role in adolescence with CFS. Therefore, in this study, we investigated the differential expression of 5 miRNAs previously evaluated in older patients with CFS, using whole blood collected from adolescents with CFS and from HCs. Our results show that the expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143 was significantly downregulated in adolescents with CFS compared with that in HCs.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome

2019

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Background Numerous experimental models have shown that microRNAs (miRNAs)play an important role in regulating pain processing in clinical pain disorders. In this study, we evaluated a set of miRNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS). We then correlated the expression of these miRNAs with the levels of inflammatory markers and pain‐related comorbidities in adolescents with CFS and healthy controls (HCs). Methods A total of 150 adolescents, 12 to 18 years of age, participated in this study between April 2016 and April 2017. The participants were classified into 2 groups: adolescents with CFS (n = 100) and HCs (n = 50). Reverse‐transcription polymerase chain reaction was used to evaluate the expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143. Immunoassay analysis was used to assess the levels of immune inflammatory markers interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and cyclooxygenase‐2 (COX‐2). Results Adolescents with CFS showed significantly higher pain thresholds than comparable nonfatigued HCs. Ability to enjoy life and relations with others were the parameters least influenced by pain in CFS patients. Differential expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143 was significantly downregulated and notably interfered with pain intensity and frequency in patients with CFS. Also, the expression of these miRNAs was significantly correlated with that of IL‐6, TNF‐α, and COX‐2, which have been shown to mediate pain intensity in patients with CFS. Girls with CFS showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CFS. Girls with CFS also showed increased expression of the inflammatory pain–related markers IL‐6, TNF‐α, and COX‐2 compared with the levels of boys with CFS. Conclusions The intensity and consequences of pain were influenced by differential expression of miR‐558, miR‐146a, miR‐150, miR‐124, and miR‐143, which was directly associated with higher expression of the immune inflammatory‐related genes TNFα, IL‐6, and COX‐2 in adolescents with CFS. Further studies of larger patient cohorts will help clarify the role of miRNAs in the pathogenesis of CFS.

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“…This miR, however, has been reported to be upregulated in plasma of CFS/ME patients [19]. It should be pointed out that the differences found across different pain models suggest the existence of disorder specific miRNAs rather than common miRNA regulators of nociceptive modulation.…”

Section: Mt Impact On the Nervous System And On Pain Reliefmentioning

confidence: 93%

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

Espejo¹,

García-Escudero²,

Oltra³

2018

Preprint

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Abstract:Application of protocols without parameter standardization and rigorous controls has led manual therapy (MT) and other physiotherapy approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way this can be achieved is by studying gene expression and additional physiological changes that associate to particular, parameter-controlled, treatments in animal models and translating this knowledge to properly design objective, quantitatively-monitored clinical trials. Here, we propose a Molecular Physiotherapy Approach (MPTA), requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports of MT that historically attribute benefits to these treatments. The review focuses in the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and CFS/ME. The systemic effect associated to mechanical-load responses is considered of particular relevance as it suggests that defined, low-pain areas could be selected for treatments with overall benefits, an aspect that might result essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to treat FM and CFS/ME.

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High-Throughput Sequencing of Plasma MicroRNA in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Cited by 39 publications

References 70 publications

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

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