scholarly journals Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ludovic Giloteaux ◽  
Adam O’Neal ◽  
Jesús Castro-Marrero ◽  
Susan M. Levine ◽  
Maureen R. Hanson
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Extracellular Vesicles ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Unknown Etiology ◽  
Cytokine Signaling ◽  
Control Group ◽  
Homogeneous Population ◽  
Fatigue Syndrome ◽  
Immune System Dysfunction

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology lasting for a minimum of 6 months but usually for many years, with features including fatigue, cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Dysregulation of cytokine signaling could give rise to many of these symptoms. Cytokines are present in both plasma and extracellular vesicles, but little investigation of EVs in ME/CFS has been reported. Therefore, we aimed to characterize the content of extracellular vesicles (EVs) isolated from plasma (including circulating cytokine/chemokine profiling) from individuals with ME/CFS and healthy controls. Methods We included 35 ME/CFS patients and 35 controls matched for age, sex and BMI. EVs were enriched from plasma by using a polymer-based precipitation method and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and immunoblotting. A 45-plex immunoassay was used to determine cytokine levels in both plasma and isolated EVs from a subset of 19 patients and controls. Linear regression, principal component analysis and inter-cytokine correlations were analyzed. Results ME/CFS individuals had significantly higher levels of EVs that ranged from 30 to 130 nm in size as compared to controls, but the mean size for total extracellular vesicles did not differ between groups. The enrichment of typical EV markers CD63, CD81, TSG101 and HSP70 was confirmed by Western blot analysis and the morphology assessed by TEM showed a homogeneous population of vesicles in both groups. Comparison of cytokine concentrations in plasma and isolated EVs of cases and controls yielded no significant differences. Cytokine-cytokine correlations in plasma revealed a significant higher number of interactions in ME/CFS cases along with 13 inverse correlations that were mainly driven by the Interferon gamma-induced protein 10 (IP-10), whereas in the plasma of controls, no inverse relationships were found across any of the cytokines. Network analysis in EVs from controls showed 2.5 times more significant inter-cytokine interactions than in the ME/CFS group, and both groups presented a unique negative association. Conclusions Elevated levels of 30-130 nm EVs were found in plasma from ME/CFS patients and inter-cytokine correlations revealed unusual regulatory relationships among cytokines in the ME/CFS group that were different from the control group in both plasma and EVs. These disturbances in cytokine networks are further evidence of immune dysregulation in ME/CFS.

scholarly journals Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

2018 ◽  
Vol 7 (1) ◽  
pp. 1453730 ◽  
Author(s):  
Jesús Castro-Marrero ◽  
Esther Serrano-Pertierra ◽  
Myriam Oliveira-Rodríguez ◽  
Maria Cleofé Zaragozá ◽  
Alba Martínez-Martínez ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chronic Fatigue Syndrome ◽  
Extracellular Vesicles ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Potential Biomarkers

scholarly journals A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction

2020 ◽  
Author(s):  
Eiren Sweetman ◽  
Torsten Kleffmann ◽  
Christina Edgar ◽  
Michel de Lange ◽  
Rosamund Vallings ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Differentially Expressed ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Fatigue Syndrome ◽  
Ms Analysis

Abstract Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious and complex physical illness that affects all body systems with a multiplicity of symptoms, but key hallmarks of the disease are pervasive fatigue and ‘post-exertional malaise’, exacerbation after physical and/or mental activity of the intrinsic fatigue and other symptoms that can be highly debilitating and last from days to months. Although the disease can vary widely between individuals, common symptoms also include pain, cognitive deficits, sleep dysfunction, as well as immune, neurological and autonomic symptoms. Typically, it is a very isolating illness socially, carrying a stigma because of the lack of understanding of the cause and pathophysiology.Methods: To gain insight into the pathophysiology of ME/CFS, we examined the proteomes of peripheral blood mononuclear cells (PBMCs) by SWATH-MS analysis in a small well-characterised group of patients and matched controls. A principal component analysis (PCA) was used to stratify groups based on protein abundance patterns, which clearly segregated the majority of the ME/CFS patients (9/11) from the controls. This majority subgroup of ME/CFS patients was then further compared to the control group. Results: A total of 60 proteins in the ME/CFS patients were differentially expressed (P < 0.01, Log10 (Fold Change) > 0.2 and < -0.2). Comparison of the PCA selected subgroup of ME/CFS patients (9/11) with controls increased the number of proteins differentially expressed to 99. Of particular relevance to the core symptoms of fatigue and post-exertional malaise experienced in ME/CFS, a proportion of the identified proteins in the ME/CFS groups were involved in mitochondrial function, oxidative phosphorylation, electron transport chain complexes, and redox regulation. A significant number were also involved in previously implicated disturbances in ME/CFS, such as the immune inflammatory response, DNA methylation, apoptosis and proteasome activation. Conclusions: The results from this study support a model of deficient ATP production in ME/CFS, compensated for by upregulation of immediate pathways upstream of Complex V that would suggest an elevation of oxidative stress. This study and others have found evidence of a distinct pathology in ME/CFS that holds promise for developing diagnostic biomarkers.

scholarly journals Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e015296 ◽  
Author(s):  
Kate E Earl ◽  
Giorgos K Sakellariou ◽  
Melanie Sinclair ◽  
Manuel Fenech ◽  
Fiona Croden ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cohort Study ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Control Group ◽  
Vitamin D Metabolites ◽  
Fatigue Syndrome ◽  
Vitamin D Levels ◽  
25 Oh Vitamin D

ObjectiveSevere vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites.DesignCohort study.SettingUK university hospital, recruiting from April 2014 to April 2015.ParticipantsNinety-two patients with CFS/ME and 94 age-matched healthy controls (HCs).Main outcome measuresThe presence of a significant association between CFS/ME, fatigue and vitamin D measures.ResultsNo evidence of a deficiency in serum total 25(OH) vitamin D (25(OH)D2and 25(OH)D3metabolites) was evident in individuals with CFS/ME. Liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis revealed that total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively). Analysis of food/supplement diaries with WinDiets revealed that the higher total 25(OH) vitamin D concentrations observed in the CFS/ME group were associated with increased vitamin D intake through use of supplements compared with the control group. Analysis of Chalder Fatigue Questionnaire data revealed no association between perceived fatigue and vitamin D levels.ConclusionsLow serum concentrations of total 25(OH)D do not appear to be a contributing factor to the level of fatigue of CFS/ME.

scholarly journals Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

2021 ◽  
Vol 18 (5) ◽  
pp. 2366
Author(s):  
Joshua Bond ◽  
Tessa Nielsen ◽  
Lynette Hodges
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Vascular Function ◽  
Augmentation Index ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Control Group ◽  
Fatigue Syndrome ◽  
The Impact

Background: Evidence is emerging that individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may suffer from chronic vascular dysfunction as a result of illness-related oxidative stress and vascular inflammation. The study aimed to examine the impact of maximal-intensity aerobic exercise on vascular function 48 and 72 h into recovery. Methods: ME/CFS (n = 11) with gender and age-matched controls (n = 11) were randomly assigned to either a 48 h or 72 h protocol. Each participant had measures of brachial blood pressure, augmentation index (AIx75, standardized to 75 bpm) and carotid-radial pulse wave velocity (crPWV) taken. This was followed by a maximal incremental cycle exercise test. Resting measures were repeated 48 or 72 h later (depending on group allocation). Results: No significant differences were found when ME/CFS were directly compared to controls at baseline. During recovery, the 48 h control group experienced a significant 7.2% reduction in AIx75 from baseline measures (p < 0.05), while the matched ME/CFS experienced no change in AIx75. The 72 h ME/CFS group experienced a non-significant increase of 1.4% from baseline measures. The 48 h and 72 h ME/CFS groups both experienced non-significant improvements in crPWV (0.56 ms−1 and 1.55 ms−1, respectively). Conclusions: The findings suggest that those with ME/CFS may not experience exercise-induced vasodilation due to chronic vascular damage, which may be a contributor to the onset of post-exertional malaise (PEM).

scholarly journals Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis

2021 ◽  
Vol 15 ◽  
Author(s):  
Adonis Sfera ◽  
Carolina Osorio ◽  
Carlos M. Zapata Martín del Campo ◽  
Shaniah Pereida ◽  
Steve Maurer ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Viral Infections ◽  
Life Quality ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Unknown Etiology ◽  
Host Proteins ◽  
Fatigue Syndrome ◽  
Long Time ◽  
Sleep Abnormalities

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.

scholarly journals Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

2017 ◽  
Author(s):  
Santiago Herrera ◽  
Wilfred C. de Vega ◽  
David Ashbrook ◽  
Suzanne D. Vernon ◽  
Patrick O. McGowan
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Complex Disease ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Genetic Interactions ◽  
Unknown Etiology ◽  
Immune Functioning ◽  
Fatigue Syndrome ◽  
Close Proximity

ABSTRACTMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown. In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls. We found significant associations of 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 phenotypes 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.

scholarly journals Can prolong life with nine turn method (Yan Nian Jiu Zhuan) Qigong alleviates Fatigue, Sleep quality, Depression and anxiety on Patients with Chronic Fatigue Syndrome: a Randomized, Controlled, Clinical Study ?

2021 ◽  
Author(s):  
Fangfang Xie ◽  
Jiatuo Xu ◽  
Chong Guan ◽  
Ziji Cheng ◽  
Yuanjia Gu ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Sleep Quality ◽  
Chronic Fatigue ◽  
Anxiety And Depression ◽  
Unknown Etiology ◽  
Control Group ◽  
Depression And Anxiety ◽  
Treatment Groups ◽  
Fatigue Syndrome ◽  
Wide Range

Abstract Background Chronic fatigue syndrome (CFS) is a complex disease with unknown etiology and mechanism. Prolong life with nine turn method (PLWNT) Qigong is a system of mind-body exercise with restorative benefits that have shown a wide range of benefits in the treatment of CFS. The purpose of this study is to investigate the effect of PLWNT Qigong exercise on CFS with a focus on fatigue, sleep quality, depression and anxiety. Methods A total of 135 participants were randomly divided into treatment groups and control group in the same proportion. The treatment groups received PLWNT Qigong exercise (PLWNT Group) or cognitive behavioral therapy treatment (CBT Group). The healthy control group (HC Group) does not receive any treatment and maintains daily life. Participants from treatment groups were taught by related highly qualified professor at the Shanghai University of Traditional Chinese Medicine once a week and were supervised online during the remaining 6 days at home, over 12 consecutive weeks. The primary outcome was fatigue (MFI-20) and secondary outcomes were sleep quality (PSQI), anxiety and depression (HADS). All groups were measured at baseline (T0) and post-intervention (T1). Results 134 patient completed the study (45 in the PLWNT Group, 44 in the CBT Group and 45 in HC Group). The within group comparison of PLWNT and CBT groups were all showed significant improvement in MFI-20, PSQI and HADS after the intervention (p༜0.05). No significant difference was found between the PLWNT group and CBT group(p༞0.05),but the total effective rate of the PLWNT group was 62.22%, which was higher than the CBT group was 50.00%. The changes in the PLWNT group and CBT group were all higher than those in the HC group except for habitual sleep efficiency and sleep medicine using(p༜0.05). In additional, fatigue degree changes in the PLWBT group were positively correlated with sleep degree (r=0.315) and anxiety degree(r=0.333), but only anxiety degree(r=0.332) was found to be positively correlated with fatigue in the CBT group. Conclusion PLWNT Qigong exercise has the potential as a rehabilitation method on CFS with a focus on fatigue, sleep quality, anxiety and depression. Yet, the results need to be interpreted carefully and needs to be repeated in a larger sample. Future studies will expand the sample size for further in-depth research to determine the frequency and intensity of PLWNT Qigong intervention that is particularly beneficial to CFS. The study registered in the American Clinical Trial Registry on 4 November 2018, the registration number is NCT03496961.

scholarly journals Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

2019 ◽  
Author(s):  
Ece Karhan ◽  
Courtney L Gunter ◽  
Vida Ravanmehr ◽  
Meghan Horne ◽  
Lina Kozhaya ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Fatigue Syndrome ◽  
Cell Subset ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
T Cell Subsets ◽  
Unknown Etiology ◽  
T Cell Subset ◽  
Fatigue Syndrome

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder of unknown etiology, and diagnosis of the disease is largely based on clinical symptoms. We hypothesized that immunological disruption is the major driver of this disease and analyzed a large cohort of ME/CFS patient or control blood samples for differences in T cell subset frequencies and functions. We found that the ratio of CD4+ to CD8+ T cells and the proportion of CD8+ effector memory T cells were increased, whereas NK cells were reduced in ME/CFS patients younger than 50 years old compared to a healthy control group. Remarkably, major differences were observed in Th1, Th2, Th17 and mucosal-associated invariant T (MAIT) T cell subset functions across all ages of patients compared to healthy subjects. While CCR6+ Th17 cells in ME/CFS secreted less IL-17 compared to controls, their overall frequency was higher. Similarly, MAIT cells from patients secreted lower IFNγ, GranzymeA and IL-17 upon activation. Together, these findings suggest chronic stimulation of these T cell populations in ME/CFS patients. In contrast, the frequency of regulatory T cells (Tregs), which control excessive immune activation, was higher in ME/CFS patients. Finally, using a machine learning algorithm called random forest, we determined that the set of T cell parameters analyzed could identify more than 90% of the subjects in the ME/CFS cohort as patients (93% true positive rate or sensitivity). In conclusion, these multiple and major perturbations or dysfunctions in T cell subsets in ME/CFS patients suggest potential chronic infections or microbiome dysbiosis. These findings also have implications for development of ME/CFS specific immune biomarkers and reveal potential targets for novel therapeutic interventions.

scholarly journals Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 98
Author(s):  
C. (Linda) M. C. van Campen ◽  
Frans C. Visser
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Case Control Study ◽  
Orthostatic Intolerance ◽  
Chronic Fatigue ◽  
Case Control ◽  
Myalgic Encephalomyelitis ◽  
Control Group ◽  
Postural Orthostatic Tachycardia Syndrome ◽  
Fatigue Syndrome ◽  
Control Study

Background and objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Exact numbers on syncopal spells especially if they are on a weekly or even daily basis are not described. Although not a frequent phenomenon, this symptomatology is of very high burden to the patient if present. To explore whether patients with very frequent (pre)syncope spells diagnosed elsewhere with conversion or psychogenic pseudosyncope (PPS) might have another explanation of their fainting spells than behavioral psychiatric disorders, we performed a case–control study comparing ME/CFS patients with and without PPS spells. Methods and results: We performed a case–control study in 30 ME/CFS patients diagnosed elsewhere with PPS and compared them with 30 control ME/CFS patients without syncopal spells. Cases were gender, age and ME/CFS disease duration matched. Each underwent a tilt test with extracranial Doppler measurements for cerebral blood flow (CBF). ME/CFS cases with PPS had a significant larger CBF reduction at end tilt than controls: 39 (6)% vs. 25 (4)%; (p < 0.0001). Cases had more severe disease compared with controls (chi-square p < 0.01 and had a p = 0.01) for more postural orthostatic tachycardia syndrome in cases compared with controls. PETCO2 end-tilt differed also, but the magnitude of difference was smaller than compared with the CBF reduction: there were no differences in heart rate and blood pressure at either end-tilt testing period. Compared with the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 25 (5) mmHg versus 29 (4) mmHg (p < 0.005). Conclusions: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background.

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