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Hardcastle, Sharni Lee; Brenu, Ekua; Wong, Naomi; Johnston, Samantha; Nguyen, Thao; Huth, Teilah Kathryn; Hawthorn, Ally; Passmore, Rachel; Ramos, Sandra Bahia; Salajegheh, Ali; Staines, Donald; Marshall‐Gradisnik, Sonya

doi:10.1016/j.cyto.2014.07.081

Cited by 2 publications

(1 citation statement)

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“…IL8 has already been observed as the gene most differentially expressed between ME/CFS and controls (7,30). Other previous studies also having observed a significantly higher level of IL-8 in severely affected ME/CFS patient group compared to both healthy controls and moderately affected ME/CFS patients (31).…”

Section: Immune and Inflammatory Changes Implicated In Relapse-recove...mentioning

confidence: 79%

Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Helliwell

Stockwell

Edgar

et al. 2022

Preprint

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(242) Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease with variable severity throughout the ongoing illness. Patients experience relapses where symptoms increase in severity, leaving them with a marked reduction in quality of life. Previous work has investigated molecular differences between ME/CFS patients and healthy controls, but the dynamic changes specific to each individual patient are unknown. Precision medicine can determine how each patient responds individually during variations in their long-term illness. We apply precision medicine here to map genomic changes in two selected ME/CFS patients through a relapse recovery cycle. Results DNA was isolated from Peripheral Blood Mononuclear Cells (PBMCs) from two patients and a healthy age/gender matched control in a longitudinal study to capture a patient relapse. Reduced representation DNA methylation sequencing profiles were obtained from each time point spanning the relapse recovery cycle. Both patients throughout the time course showed a significantly larger methylome variability (10-20 fold) compared with the control. During the relapse changes in the methylome profiles of the two patients were detected in regulatory-active regions of the genome that were associated respectively with 157 and 127 downstream genes, indicating disturbed metabolic, immune and inflammatory functions occurring during the relapse. Conclusions Severe health relapses in ME/CFS patients result in functionally important changes in their DNA methylomes that, while differing among patients, lead to similar compromised physiology. DNA methylation that is a signature of disease variability in ongoing ME/CFS may have practical applications for strategies to decrease relapse frequency.

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Section: Immune and Inflammatory Changes Implicated In Relapse-recove...mentioning

confidence: 79%

Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Helliwell

Stockwell

Edgar

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients

2016

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BackgroundNatural Killer (NK) cell effector functions are dependent on phosphorylation of the mitogen-activated protein kinases (MAPK) pathway to produce an effective immune response for the clearance of target cells infected with viruses, bacteria or malignantly transformed cells. Intracellular signals activating NK cell cytokine production and cytotoxic activity are propagated through protein phosphorylation of MAPKs including MEK1/2, ERK1/2, p38 and JNK. Reduced NK cell cytotoxic activity is consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients and intracellular signalling by MAPK in NK cells remains to be investigated. Therefore, the purpose of this paper was to investigate MAPK downstream signalling molecules in NK cell phenotypes from CFS/ME patients.MethodsFlow cytometric protocols were used to measure phosphorylation of the MAPK pathway in CD56brightCD16dim/− and CD56dimCD16+ NK cells following stimulation with K562 tumour cells or phorbol-12-myristate-13-acetate plus ionomycin. NK cell cytotoxic activity, degranulation, lytic proteins and cytokine production were also measured as markers for CD56brightCD16dim/− and CD56dimCD16+ NK cell function using flow cytometric protocols.ResultsCFS/ME patients (n = 14) had a significant decrease in ERK1/2 in CD56dimCD16+ NK cells compared to the non-fatigued controls (n = 11) after incubation with K562 cells. CD56brightCD16dim/− NK cells from CFS/ME patients had a significant increase in MEK1/2 and p38 following incubation with K562 cells.ConclusionsThis is the first study to report significant differences in MAPK intracellular signalling molecules in CD56dimCD16+ and CD56brightCD16dim/− NK cells from CFS/ME patients. The current results highlight the importance of intracellular signalling through the MAPK pathway for synergistic effector function of CD56dimCD16+ and CD56brightCD16dim/− NK cells to ensure efficient clearance of target cells. In CFS/ME patients, dysfunctional MAPK signalling may contribute to reduced NK cell cytotoxic activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0859-z) contains supplementary material, which is available to authorized users.

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74

Cited by 2 publications

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Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients

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