HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entity
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ABSTRACT:
PROVIDER: PRJNA1120018 | ENA |
REPOSITORIES: ENA
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Project description:Research of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance and etiology. Despite prior detection of human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value of HERV expression profiles for their diagnosis, and the relationship of HERV expression profiles with patient immune systems and symptoms had remained unexplored. By using HERV-V3 high-density microarrays (including over 350k HERV elements and more than 1500 immune-related genes) to interrogate the transcriptomes of peripheral blood mononuclear cells from female patients diagnosed with ME/CFS, FM or both, and matched healthy controls (n=43), this study fills this gap of knowledge. Hierarchical clustering of HERV expression profiles strikingly allowed perfect participant assignment into four distinct groups: ME/CFS, FM, co-diagnosed, or healthy, pointing at a potent biomarker value of HERV expression profiles to differentiate between these hard-to-diagnose chronic syndromes. Differentially expressed HERV-immune-gene modules revealed unique profiles for each of the four study groups and highlighting decreased γδ T cells, and increased plasma and resting CD4 memory T cells, correlating with patient symptom severity in ME/CFS. Moreover, activation of HERV sequences coincided with enrichment of binding sequences targeted by transcription factors which recruit SETDB1 and TRIM28, two known epigenetic silencers of HERV, in ME/CFS, offering a mechanistic explanation for the findings. Unexpectedly, HERV expression profiles appeared minimally affected in co-diagnosed patients denoting a new nosological entity with low epigenetic impact, a seemingly relevant aspect for the diagnosis and treatment of this prevalent group of patients.
2025-03-01 | GSE269047 | GEO
Project description:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia. We quantified a total of 2,083 proteins using immunoaffinity depletion, tandem mass tag isobaric labeling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1,789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p-value < 0.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.
2022-11-09 | MSV000090685 | MassIVE
Project description:The endogenous retrovirus type W (HERV-W) is a human specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted ex vivo, given the human specific origin of HERV-W. Recent experimental evidence gathered on a novel transgenic mouse model, mimicking activation and expression of the HERV-W ENV protein, revealed that all glial cell types are impacted and that cellular fates, differentiation, and functions were changed. In order to identify a HERV-W specific signature in glial cells, the current study analyzed the transcriptome of ENV stimulated microglial- and astroglial cells and compared the transcriptomic signature to lipopolysaccharide (LPS) stimulated cells, owing to the fact that both ligands can activate toll-like receptor-4 (TLR-4). Additionally, a comparison between published disease associated glial signatures and the transcriptome of HERV-W ENV stimulated glial cells was conducted. We, therefore, provide here for the first time a detailed molecular description of specific HERV-W ENV evoked effects on those glial cell populations that are involved in smoldering neuroinflammatory processes relevant for progression of neurodegenerative diseases.
2024-03-30 | GSE262029 | GEO
Project description:Fibromyalgia (FM), classified by ICD-11 with code MG30.0, is a chronic debilitating disease characterized by wide-spread pain, fatigue, cognitive impairment, sleep and intestinal alterations, among other. FM affects a large proportion of the world-wide population, with increased prevalence among women. The lack of understanding of its etiology and pathophysiology hampers the development of effective treatments. Our group had developed a manual therapy (MT) pressure-controlled custom manual protocol on FM showing hyperalgesia/allodynia, fatigue and patient’s quality of life benefits in a cohort of 38 FM cases (NCT04174300). With the aim of understanding the therapeutic molecular mechanisms triggered by MT, this study interrogated PBMC transcriptomes from FM participants of this clinical trial using RNAseq and RT-qPCR technologies. The results showed that the salt-induced kinase SIK1 gene was consistently downregulated by MT in FM, correlating with improvement of patient symptoms. In addition, the study compared the findings in a non-FM control cohort subjected to the same MT protocol evidencing that changes in SIK1 expression with MT only occurred in individuals with FM. This positions SIK1 as a potential biomarker to monitor response to MT, and as a therapeutic target of FM, to be further explored by continuation studies. Keywords: fibromyalgia; myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); pressure point threshold (PPT); physiotherapy; manual therapy (MT); NCT04174300; SIK1
2024-09-11 | GSE274134 | GEO
Project description:Fibromyalgia is a chronic pain syndrome characterized by widespread pain. The pathophysiology of fibromyalgia is not clearly understood and there are no specific biomarkers available for accurate diagnosis. Here we define genomic signatures using high throughput RNA sequencing on 96 fibromyalgia and 93 matched controls. Our findings revealed two major fibromyalgia-associated expression signatures. The first group included 44 patients with a signature enriched for gene expression associated with extracellular matrix and downregulation of RhoGDI signaling pathway. The second group included 31 patients and showed a profound reduction in the expression of inflammatory mediators with an increased expression of genes involved in the CLEAR signaling pathway. These results suggest defective tissue homeostasis associated with the extra-cellular matrix and cellular program that regulates lysosomal biogenesis and participates in macromolecule clearance in fibromyalgia. Further elucidation of these pathways will lead to development of accurate diagnostic markers, and effective therapeutic options for fibromyalgia.
2024-02-21 | GSE221921 | GEO
Project description:The HERV-K(HML2) family is a group of elements of retroviral origin that are present in the human genome. They are silenced in most normal tissues, but are induced in a number of human cancers. In order to assess the relevance of their expression in these pathologies, the consequences of ectopic expression of the HERV-K(HML2) envelope protein were analysed in human 293T cells. The cells were transfected with a control vector, or an expression vector for the HERV-K(HML2) envelope protein. Total RNA was extracted 24h and 48h post transfection, and duplicate samples were analysed on whole genome transcriptional microarrays.
2017-06-17 | E-MTAB-5509 | biostudies-arrayexpress
Project description:FM is a complex syndrome with physiological, genetics and environmental factors involved. It can present changes in functional neuroimaging, in cortical excitability measurements performed by transcranial magnetic stimulation and in grey matter density. Similarly, it has been shown that patients with FM have abnormal autonomic control, inflammatory profile and dysfunctional hypothalamic–pituitary–adrenal axis leading to disruptive sleep and fatigue. We characterized clinical and neurophysiological parameters and peripheral blood DNA methylation profiles of patients with FM and compared them to sex and age matched healthy controls. We hypothesized that these exploratory analyses could provide mechanistic insights into the pathophysiology of FM and possibly contribute to the future development of biological markers of diagnosis.We showed that patients with fibromyalgia have different (mainly hypo-) methylated CpG sites related to genes implicated in immune system and response to external stress pathways and that this methylation profile is related to a dysfunctional connectivity in pain network, adding evidence to consider fibromyalgia as a DOHAD disorder.
2017-08-10 | GSE85506 | GEO
Project description:Provide a comprehensive picture of HERV RNA expression through both short and long read sequencing in NCCIT cells to be used in an integrated proteogenomic analysis pipeline
2025-01-08 | PXD054413 | Pride
Project description:To investigate the cancer properties of HERV-R knockout in the colon cancer cell line DLD1, we knocked out HERV-R from Crispr-cas9 in DLD1. We performed RNA-seq to profile gene expression in DLD1, DLD1R (HERV-R KO) cells, respectively.
2025-01-08 | GSE285815 | GEO