Proteomics profiling of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Blood Cell, Blood Plasma
DISEASE(S): Mixed Disorder As Reaction To Stress
SUBMITTER: 
Bohyun Lee
LAB HEAD: W. Ian Lipkin
PROVIDER: PXD016622 | Pride | 2020-07-07
REPOSITORIES: Pride
Dataset's files
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Publications
Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS.
Milivojevic Milica M Che Xiaoyu X Bateman Lucinda L Cheng Aaron A Garcia Benjamin A BA Hornig Mady M Huber Manuel M Klimas Nancy G NG Lee Bohyun B Lee Hyoungjoo H Levine Susan S Montoya Jose G JG Peterson Daniel L DL Komaroff Anthony L AL Lipkin W Ian WI
PloS one 20200721 7
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an unexplained chronic, debilitating illness characterized by fatigue, sleep disturbances, cognitive dysfunction, orthostatic intolerance and gastrointestinal problems. Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we analyzed the plasma proteomes of 39 ME/CFS patients and 41 healthy controls. Logistic regression models, with both linear and quadratic terms of the protein levels as independent v ...[more]
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Project description:Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition that involves multiple organ systems and is characterized by an abrupt or delayed onset of persistent/relapsing symptomatology such as debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months. Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, the status of this epigenetic mark in ME/CFS remains uncertain. This study aimed at identifying changes in the DNA methylation patterns that are causative of changes in the regulation of gene expression in ME/CSF patients. Such changes may be also used for diagnostic purposes and be indicative of potential therapeutic targets. Methods: Peripheral blood mononuclear cells (PBMCs) from 13 ME/CFS patients and 12 healthy controls (HC) were used to extract genomic DNA and measure global DNA methylation, and the methylation status at 850,000 CpG sites was assessed using Illumina MethylationEPIC microarrays. Results: Global DNA methylation levels of ME/CFS patients were similar to those of HC. However, microarray-based genome-wide technology allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across promoters, gene regulatory elements and within coding regions of genes. Analysis of DNA methylation in promoter regions found 307 differentially methylated promoters (DMP); genes associated with DMP participate in at least 15 different pathways mostly related to cell signaling with a strong immune component. Conclusions: This is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the new MethylationEPIC microarrays covering about 850,000 CpG sites. Our results are consistent with dysregulation of the immune system in ME/CFS and suggest a role of this epigenetic modification on the DNA pathobiology of ME/CFS.
2018-07-23 | GSE111183 | GEO
Project description:We conducted a microarray study of sigmoid mucosal gene expression in pilot sample of Rome III+ IBS patients and age and sex-matched HCs. This sample was balanced by sex, free of active psychiatric disease and had limited use of medications. Rome III+ IBS patients and HCs ages 18-55 were recruited primarily by community advertisement. Bowel habit subtypes (IBS with diarrhea (IBS-D), constipation (IBS-C) and mixed pattern (IBS-M)) were based on the Rome III criteria. The diagnosis was confirmed by a clinician with expertise in IBS. Rome III+a IBS patients and HCs ages 18-55 were recruited primarily by community advertisement. Bowel habit subtypes (IBS with diarrhea (IBS-D), constipation (IBS-C) and mixed pattern (IBS-M)) were based on the Rome III criteria. The diagnosis was confirmed by a clinician with expertise in IBS. HCs had no personal or family history of IBS or other chronic pain conditions. Additional exclusion criteria for all subjects included: infectious or inflammatory disorders, active psychiatric illness over the past 6 months as assessed by structured clinical interview for the DSM-IV (MINI),b use of corticosteroids in the past six months, use of narcotics, antidepressants or other medications that could affect neuroendocrine function in the past two months, or current tobacco or alcohol abuse. Participants were compensated. Our goal was to evaluate women during the follicular phase or days 4-14 of their menstrual cycle if on oral contraceptive pills. Phase was determined by date of last menstrual period and progesterone levels. The study was approved by the UCLA Institutional Review Board, and all subjects signed a written informed consent prior to start of study. IBS symptom severity over the prior week was assessed with a numeric rating scale (0-20).c Current anxiety and depression symptoms were measured with the Hospital Anxiety and Depression (HAD) scale.d Sigmoid biopsies (30cm from the anal verge) were obtained by flexible sigmoidoscopy following tap water enemas. Specimens were immediately flash frozen in liquid nitrogen. RNA was extracted with TRIzol. Sigmoid biopsies (30cm from the anal verge) were obtained by flexible sigmoidoscopy following tap water enemas. Specimens were immediately flash frozen in liquid nitrogen. Differential expression analysis was done on mRNA only (\\ormalized_Unfiltered_mRNAonly.txt\\) using limma[1]. Weighted gene coexpression network analysis (WGCNA[2]) was done using all targets after removing those on X and Y chromosomes and filtered by mean raw signal >200. 1. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:Article3. 2. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.\
2018-06-03 | E-MTAB-5811 | biostudies-arrayexpress
Project description:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, potential interactions between DNA methylation and genetic background in relation to ME/CFS have not been examined. In this study we explored this association by characterizing the epigenetic (~480 thousand CpG loci) and genetic (~4.3 million SNPs) variation between cohorts of ME/CFS patients and healthy controls. We found significant associations of DNA methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation modifications associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.
2020-08-25 | GSE156792 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-12-22 | GSE251790 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing in 35 ME/CFS patients (24 female, 11 male) and 34 matched healthy control participants (21 female and 13 male) during and after an exercise challenge intended to provoke PEM. The effects of exertion in the male ME/CFS cohort highlighted pathways related to immune cell signaling (including IL-12) and NK cell cytotoxicity, while female ME/CFS patients did not have significant enough changes in gene expression to meet criteria for our study. Functional analysis during recovery from exercise showed that male ME/CFS patients had distinct changes in regulation of specific cytokine signals (including IL-1β). Female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses and NF-kβ signaling. The functional pathways and differentially expressed genes highlighted in this study provide insight into sex-specific predisposition and pathophysiology of ME/CFS.
2023-06-19 | GSE227375 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2024-01-24 | GSE254030 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-10-31 | GSE245661 | GEO
Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder that may occur following an infection, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit a cohort of post-infectious ME/CFS (PI-ME/CFS) volunteers (n=17) with matched healthy controls (n=21) to conduct deep clinical and biological phenotyping using an extensive battery of tests. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical deconditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
2023-12-22 | GSE251872 | GEO
Project description:Purpose: ME/CFS is a debilitating and complex disease. The majority of patients exist in a chronic state of health where they are affected by relapse events. Precision medicine following patients can capture changes in the DNA methylation indicative of biological dysfunction Methods: DNA was extracted from the PBMCs of 2 ME/CFS patients and a age/gender matched control at five different time points. After performing RRBS the sequence was aligned to hg19 genome using Bismark. The data was analyzed using a Chi squared test through DMAP in order to determine variation between the patient and control groups across 40-220bp fragments of the genome. Results: A total of 17 and 14 statistically significant variably methylated fragements were indentified in each patient that strongly associated with a relapse event. These fragements were found on regions of regulatory importance of the genome that associated with immune (primarily inflammatory) and metabolic function. Conclusions: Our study represents the first investigation of ME/CFS patients using reduced representation bisulfite sequencing along a longitudinal timeframe. We captured a number of major variably methylated fragments in each patient that associated with their relapse events. Our results identified a number of differentially methylated regulatory elements and gene bodies that highlight the disturbed pathophysiology in ME/CFS. DNA methylation that differentiates disease variability in ongoing ME/CFS may have practical applications for strategies to deacrease the frequency and severity of relapse events.
2021-02-11 | GSE166592 | GEO
Project description:Purpose: ME/CFS is a lifelong debilitating disease that affects approximately 1% of the global population. Previous studies have identified dysfunctional activity in metabolic, immune and neurological pathways. The goal of this study is to identify ME/CFS specific variations in DNA methylation to determine whether the patient specific epigenetic patterns provide insight into the disease pathophysiology. Methods: DNA was extracted from the PBMCs of 10 ME/CFS patients and age/gender matched controls. After performing RRBS the sequence was aligned to hg19 genome using Bismark. The data was analyzed using first an ANOVA F test through DMAP in order to determine variation between the patient and control groups across 40-220bp fragments of the genome. Additional analysis was performed following a MethylKit pipeline, which analyzed the variation on a single CpG basis using a Fishers test. Results: From a total of 146,575 DMAP fragments we identified 76 differentially methylated fragments (P <0.05, Diff meth +/- 15%). A total of 31 were associated with gene regions (intronic/exonic). MethylKit analysis also identified a total of 394 differentially methylated cytosines (FDR corrected P <0.05, Diff meth +/- 15%) from a total of 196,172 individual analyzed cytosines, 91 of the statistically significant cytosines fell within gene regions. Comparison of both methylomes and regions where both the DMAP fragments and multiple MethylKit cytosines fell highlighted areas of the genome containing regulatory elements associated with metabolic and immune activity. Gene body pathway enrichment additionally identified immune metabolic and neurological related functions. Conclusions: Our study represents the first investigation of ME/CFS patients using reduced representation bisulfite sequencing. We identified a number of major differences between patients that distinguished them from healthy controls. Our results identified a number of differentially methylated regulatory elements and gene bodies that highlight the disturbed pathophysiology in ME/CFS. In particular the large number of enriched neurotransmitter and neuropeptide reactome pathways highlighted a disturbed neurological pathophysiology in patients.
2020-07-02 | GSE153667 | GEO