Inflammation and interferon signature in peripheral B-lymphocytes and sera of individuals with fibromyalgia
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ABSTRACT:
PROVIDER: PRJEB50644 | ENA |
REPOSITORIES: ENA
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Project description:Fibromyalgia (FM) is an idiopathic chronic disease characterized by widespread musculoskeletal pain, hyperalgesia and allodynia, often accompanied by fatigue, cognitive dysfunction and other symptoms. Autoimmunity and neuroinflammatory mechanisms have been suggested to play important roles in the pathophysiology of FM supported by recently identified interferon signatures in affected individuals. However, the contribution of different components in the immune system, such as the B-lymphocytes, in the progression to FM are yet unknown. Furthermore, there is a great need for biomarkers that may improve diagnostics of FM. Herein, we investigated the gene expression profile in peripheral B-cells, as well as a panel of inflammatory serum proteins, in 30 FM patients and 23 healthy matched control individuals. RNA sequence analysis revealed 60 differentially expressed genes when comparing the two groups. The group of FM patients showed increased expression of twenty-five interferon-regulated genes, such as S100A8 and S100A9, VCAM, CD163, SERPINA1, ANXA1, and an increased interferon score. Furthermore, FM was associated with elevated levels of 19 inflammatory serum proteins, such as IL8, AXIN1, SIRT2 and STAMBP, that correlated with the FM severity score. Together, the results shows that FM is associated with an interferon signature in B-cells and increased levels of a set of inflammatory serum proteins. Our findings bring further support for immune activation in the pathogenesis of FM and highlight candidate biomarkers for diagnosis and intervention in the management of FM.
| S-EPMC9177944 | biostudies-literature
Project description:To identify changes in miRNA expression profiles (miRNome) of fibromyalgia patients for the development of a quantitative diagnostic method of FM. 20% of the miRNAs analyzed (233/1212) showed down-regulation of at least 2-fold in patients. Hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p, hsa-miR145-5p and hsa-miR-21-5p were at least 4-fold inhibited.
2015-06-01 | GSE65033 | GEO
Project description:Fibromyalgia (FM) is a common pain disorder characterized by dysregulation in the processing of pain. Although FM has similarities with other rheumatologic pain disorders, the search for objective markers has not been successful. In the current study we analyzed gene expression in the whole blood of 70 fibromyalgia patients and 70 healthy matched controls. Global molecular profiling revealed an upregulation of several inflammatory molecules in FM patients and downregulation of specific pathways related to hypersensitivity and allergy. There was a differential expression of genes in known pathways for pain processing, such as glutamine/glutamate signaling and axonal development. We also identified a panel of candidate gene expression-based classifiers that could establish an objective blood-based molecular diagnostic to objectively identify FM patients and guide design and testing of new therapies. Ten classifier probesets (CPA3, C11orf83, LOC100131943, RGS17, PARD3B, ANKRD20A9P, TTLL7, C8orf12, KAT2B and RIOK3) provided a diagnostic sensitivity of 95% and a specificity of 96%. Molecular scores developed from these classifiers were able to clearly distinguish FM patients from healthy controls. An understanding of molecular dysregulation in fibromyalgia is in its infancy; however the results described herein indicate blood global gene expression profiling provides many testable hypotheses that deserve further exploration.
2016-02-01 | GSE67311 | 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: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:Fibromyalgia is a complex disorder whose main symptoms are chronic widespread pain and fatigue, and affects between 0.2 and 6.6% of the world population. Nowadays, there are no molecular biomarkers which could facilitate diagnosis, underlining the extreme necessity of basic research on this chronic disorder. The latest efforts by the researchers have focused on studying problems at the level of central nervous system sensitivity, inflammatory and oxidative disorders, and even imbalances related to the intestinal microbiota. A total of 892 women were initially enrolled in the study. For those fulfilling inclusion criteria, a plasma proteome analysis in blood samples was conducted. Briefly, blood was collected, centrifuged and analyzed by liquid nano-chromatography coupled to tandem mass spectrometry. After the raw data analysis, proteins with statistically significant differential abundance and a fold change over 1.2 (20% increase in fibromyalgia compared with control samples) or under 0.8 (20% decrease in fibromyalgia compared with control samples) in fibromyalgia were selected. For fecal metagenome analysis, fecal samples were collected, homogenized and processed for DNA extraction. Amplicon sequencing of V3–V4 regions from the 16S ribosomal RNA gene was performed using the Illumina MiSeq platform Quality control procedures were implemented using thresholds set at 50,000 reads per sample, Q30 Phred Score and an average trimmed read length of 280bp. The statistical analysis was conducted using R v4.3.2 base packages. After applying exclusion criteria, 242 women (199 patients and 43 age- and environmentally paired healthy individuals) provided plasma and feces samples, as well as properly filled health questionnaires. A total of 30 proteins and 19 taxa were differentially expressed in fibromyalgia patients, and its integration into an algorithm allows to discriminate cases and controls. The multiomic approach for biomarker discovery in this study propose a multifactorial connection between gut microbiota and mitochondria-derived oxidative stress and inflammation. Plasma and fecal multiomics analysis suggest an intricate and multifactorial connection between gut microbiota and mitochondria-derived oxidative stress and inflammation in FM patients, with glyceraldehyde-3-phosphate dehydrogenase and Streptococcus salivarius as leading actors.
2025-09-18 | PXD059894 | Pride
Project description:Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome.
2018-04-25 | PXD008076 | Pride
Project description:Fibromyalgia Microbiome Analysis: data from Ebiomedicine paper "Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia" by Clos-Garcia, M. et al.
| PRJEB27227 | ENA
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 complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown.
In this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors.
A few of the included samples have been also included in a previous GWAS study.
| EGAS00001003826 | EGA