Trial Report Sex-Dependent Transcriptional Changes in Response to Stress in Patients with ME/CFS: A Pilot Study, 2023, Nathanson, Klimas et al

Full title:
Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project

Abstract
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 (RNA-Seq) in 33 ME/CFS patients (20 female, 13 male) and 34 matched healthy controls (20 female and 14 male) before, during, and after an exercise challenge intended to provoke PEM.

Our findings revealed that pathways related to immune-cell signaling (including IL-12) and natural killer cell cytotoxicity were activated as a result of exertion in the male ME/CFS cohort, while female ME/CFS patients did not show significant enough changes in gene expression to meet the criteria for the differential expression.

Functional analysis during recovery from an exercise challenge showed that male ME/CFS patients had distinct changes in the regulation of specific cytokine signals (including IL-1β). Meanwhile, female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses, and NF-κβ signaling. The functional pathways and differentially expressed genes highlighted in this pilot project provide insight into the sex-specific pathophysiology of ME/CFS.

https://www.mdpi.com/1422-0067/24/12/10255

 

Wouldn't a larger study be necessary to "provide insight into the sex-specific pathophysiology of ME/CFS"?

 

Looks like a sort of companion study to this one?

Would have been helpful if they had presented the data in more graphic form. The narrative version employed reads to me like an endless string of "group A had increased P, group D had had decreased N, group B had decreased L, group C had increased W, etc etc etc" Just impossible for my brain to compute. Hoping somebody else can provide a summary of findings beyond what I could glean, which is - spoiler alert - men and women are different, somehow

To be fair they call it a pilot study. Bigger numbers would increase confidence in the findings but I guess there were the usual funding limits. Have to hope that other teams do similar enough studies that data can be combined in a meta-analysis later. And that other groups can extend the testing period to beyond 4 hours after CPET and make sure their controls are suitably unfit (not sure if that was done in this study).

It's encouraging we're seeing more studies looking deeply into the molecular recovery process from exercise.

Would be good if similar studies could also be done following an orthostatic stressor and a cognitive stressor.