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Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome... (Gamer et al, 2023)


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


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.



This is a great study, and @Cort has written it up part of it in a useful way at his blog.


My favourite aspect is this:

"The problem appears to be less that ME/CFS patients’ systems are responding in strange ways to exercise than that they’re not responding at all. Whatever switch gets turned on in the body to allow humans to tolerate and benefit from exercise – it’s not happening on multiple levels in ME/CFS."

two Klimas studies have both found that our bodies are just not reacting to exercise. The normal responses you'd hope to see in terms of blood proteins and immune signatures are missing (in women, less so in men).

That's the perfect end of a thread that researchers can pull at. What I love is that it related to PEM, and to the core aspect of this damn disease - that we seem to react so weirdly to exercise.

I bet if they keep looking they can find something that's supposed to rise in exercise but doesn't that is measurable easily. (via a fingerprick test?) Then we can use that as a proxy for finding what treatments work. Measurable differences are key for progress.