Dynamic Epigenetic Changes during a Relapse and 2 Recovery Cycle in ME/CFS (Helliwell et al, 2022)

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Preprint paper here:

https://www.medrxiv.org/content/10.1101/2022.02.24.22270912v1

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.
Any thoughts? It looks promising but my knowledge of epigenetics isnt deep enough to figure out how it helps. Can we get individually tested anywhere?
 

Pyrrhus

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Thanks for posting this preprint from Warren Tate's group!

There is a previous article by the same authors, which might inform this paper:

Changes in DNA methylation profiles of [ME/CFS] patients reflect systemic dysfunctions (Helliwell et al. 2020)
https://forums.phoenixrising.me/thr...emic-dysfunctions-helliwell-et-al-2020.81953/

P.S.
Here's the full abstract of the new preprint in case anyone's interested:
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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It was really fun to drag myself out of bed, crawl to the living room to announce to my spouse that at least 157 genes and maybe 127 more genes are being subjected to epigenetic alterations.