Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

Almenar-Pérez, Eloy; Ovejero, Tamara; Sánchez-Fito, Teresa; Espejo, José Andrés; Nathanson, Lubov; Oltra, Elisa

doi:10.1016/j.clinthera.2019.02.012

Cited by 23 publications

(26 citation statements)

References 129 publications

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“…As previously published by our group, it seems possible that the activation of particular patterns of transposable elements (TEs) associating with ME/CFS epigenetic marks may trigger ME/CFS patient flu-like symptoms in the absence of concomitant active infections [34]. Further work after this publication by Dr. Romano s group at the Universidade de Sao Paulo in Brazil, in fact supports that the levels of the endogenous retrovirus HERV-K are upregulated in ME/CFS.…”

Section: Introductionsupporting

confidence: 67%

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

Ovejero

Sadones

Sánchez-Fito

et al. 2020

IJMS

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Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

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Section: Introductionsupporting

confidence: 67%

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

Ovejero

Sadones

Sánchez-Fito

et al. 2020

IJMS

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“…Recently, it was suggested that differential methylation patterns of promoters in ME/CFS would impact on the expression of nearby transposable elements, including HERVs [19]. Two reports of HERV activity in ME/CFS were published some years ago but the results were conflicting.…”

Section: Discussionmentioning

confidence: 99%

HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Rodrigues

Nali

Leal

et al. 2019

Preprint

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Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Here the expression of Endogenous retroviruses K and W (HERV–K and HERV–W) was determined in blood from moderately and severely affected ME/CFS patients. HERV-K was overexpressed only in moderately affected individuals and HERV-W showed no difference. This is the first report about HERV-K differential expression in moderate ME/CFS.

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“…By contrast, the activated "cut and paste" TEs will not be retrotranscribed due to failure of fragmented tRNAs (tsRNAs) to prime [52], preserving genome integrity under a normalscenario (Figure 4). It is therefore hypothesized that an increase in long dsRNA intracellular levels in FM and ME/CFS patients deriving from epigenetic changes, as described [20][21][22][23][24][25][26][27][28][29][30][31]34], could in fact constitute a trigger for the disease in the absence of viral or other type of infection. It is perhaps the particular type of activated elements what drives the individual phenotype towards autoimmunity (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…As published, we uncovered particular patterns of transposable elements (TEs) associating with ME/CFS epigenetic marks leading to the interesting possibility that it is the activation of dormant TEs that may trigger ME/CFS patient flu-like symptoms in the absence of concomitant active infections [ 34]. Since then, the group led by Dr. Romano at the Universidade de Sao Paulo in Brazil, have informed that the levels of the endogenous retrovirus HERV-K appear in fact upregulated in ME/CFS, as shown by the analysis of PBMCs isolated from ME/CFS patients at the monographic UK ME biobank [35], supporting the hypothesis raised by our group [34]. However, and although FM frequently presents comorbid ME/CFS syndrome, no study has yet determined whether patients with a diagnosis of FM presents similar activation of this group of TEs.…”

Section: Introductionmentioning

confidence: 99%

“…Patient assessment with FIQ, MFI and SF-36[36][37][38][39] questionnaires (N=28).Based on the hypothesis that the hypomethylation patterns detected in ME/CFS and the altered miRNA levels in FM & ME/CFS may associate with aberrant activation of TEs[34], we proceeded to evaluate whether these patients present increased levels of HERVS, a subtype of TEs that can mimic infection.…”

mentioning

confidence: 99%

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Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

Ovejero¹,

Sadones²,

Sánchez-Fito³

et al. 2019

Preprint

Self Cite

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The development of nucleic acid sequencing technology and the unprecedented availability of metadata has evidenced that 45% of human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically needed. Aberrant regulation of TEs, and of human retroviral endogenous sequences (HERVs) in particular, associates with several neurologic and autoimmune diseases, including the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) frequently comorbid with fibromyalgia (FM). However, no study has yet addressed whether abnormal expression of these sequences correlates with FM. The work presented here shows, for the first time, that in fact HERVs of the H, K and W types are overexpressed in the cells of the immune system of FM patients with or without comorbid ME/CFS. The patients with increased HERV expression (N=14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. In support of our proposal that TE activation is a contributor to FM, we find that the tRNA pools are decreased in comparison to matched healthy participants (N=14). The findings reported here could explain the flu-like symptoms FM patients present with in the absence of concomitant infections. Future work towards identifying specific genomic loci differentially affected in FM and ME/CFS is granted.

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Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

Cited by 23 publications

References 129 publications

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

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