Stress-Induced Transcriptomic Changes in Females with ME/CFS Reveal Disrupted Immune Signatures, 2023, van Booven et al.

[SNT Gatchaman]

The 13-fold reduction in CD8+ T cells from maximal exertion to 4 hours after in the healthy controls is particularly remarkable, compared to no significant change in CD8+T cells in the women with ME/CFS.

I've briefly tried looking to see if such a decrease following exercise is normal, but I haven't been able to find another example.

I haven't read any of these yet, but so far I found the following refs, mostly from the last 3 years, plus a few potentially related. Feel free to peel this off to a separate thread if there's interest.

• The growing field of immunometabolism and exercise: Key findings in the last 5 years (2022, Journal of Cellular Physiology)
• Characterization of transitional memory CD4+ and CD8+ T-cell mobilization during and after an acute bout of exercise (2023, Frontiers in Sports and Active Living)
• Mastering an exhausting marathon: how CD8+ T cells fine-tune metabolic fitness (2022, Immunology and Cell Biology)
• Acute exercise impacts AhR and PD-1 levels of CD8+ T-cells—Exploratory results from a randomized cross-over trial comparing endurance versus resistance exercise (2020, European Journal of Applied Physiology)
• Acute aerobic exercise in humans increases cytokine expression in CD27− but not CD27+ CD8+ T-cells (2012, Brain, Behavior, and Immunity)

Also —

• Exercise mobilizes diverse antigen specific T-cells and elevates neutralizing antibodies in humans with natural immunity to SARS CoV-2 (2023, Brain, Behavior, & Immunity - Health)
• Impact of acute exercise on peripheral blood mononuclear cells nutrient sensing and mitochondrial oxidative capacity in healthy young adults (2021, Physiological Reports)
• Mitochondrial Mass of Naïve T Cells Is Associated with Aerobic Fitness and Energy Expenditure of Active and Inactive Adults (2022, Medicine & Science in Sports & Exercise)
  
• Influence of Exercise on Exhausted and Senescent T Cells: A Systematic Review (2021, Frontiers in Physiology)
• Exercise Attenuates M1 Macrophages and CD8+ T Cells in the Adipose Tissue of Obese Mice (2013, Medicine & Science in Sports & Exercise)

 

[DMissa]

All I can see in the abstract and conclusions are vague suppositions about regulation of some unspecified immune response. A decent paper gives you some data, without too much interpretation.

If there are interesting results here, why not tell us?

Perhaps the authors felt that the outcomes of thousands of concurrent measurements could not be fairly represented or even-handedly conveyed by only including a small selection of detailed specifics in as limited a space as an abstract or a conclusion. Seems reasonable to me if so.

 

[Hutan]

Under maximal exertion, ME/CFS patients did not show significant changes in gene expression, while HCs demonstrated altered functional gene networks related to signaling and integral functions of their immune cells. During the recovery period (commonly during onset of PEM), female ME/CFS patients showed dysregulated immune signaling pathways and dysfunctional cellular responses to stress. The unique functional pathways identified provide a foundation for future research efforts into the disease, as well as for potential targeted treatment options.

The abstract is very short though. They could have given some specific findings. I don't think the abstract serves the readers or the researchers well. It seems to lurch from generality to specificity in a way that is odd for a trial that only had female participants.

The conclusion is oddly written too:

The findings presented in our study will help to advance our understanding of the pathways and genes that are relevant to PEM and fatigue tied to ME/CFS, with the goal of identifying targets to improve diagnosis and identify more targeted therapeutic options for female ME/CFS patients.

It says that the study helps advance the understanding of ME/CFS, which is reasonable. It then suggests that the goal of such an understanding is to identify 'more targeted therapeutic options', but only for female ME/CFS patients. It's an unnecessary specificity when surely the goal is therapeutic options for all people with ME/CFS. It also suggests that there are existing untargeted therapeutic options for female ME/CFS patients.

That raises questions in my mind - did they do this study with men also, but not include those results? The methods section isn't at all reassuring (it's also not in the usual place, after the introduction, but tucked away after the discussion). No where does it tell us how many people underwent the exercise challenge.

A community-based cross-sectional study included 20 clinically diagnosed female ME/CFS subjects and 20 female healthy controls (HC) matched for age (±5 years) and BMI (±2 units). All individuals with ME/CFS and HCs were recruited from the Miami/Fort-Lauderdale area as a part of a large ongoing study by the Institute for Neuroimmune Medicine.

Part of the discussion suggests that previous studies have found different results in men and women:

In prior studies, both symptomatic and molecular differences have been elucidated between men and women diagnosed with ME/CFS [13,32,33,34]. As such, our conclusions are limited to female patients only. Further studies comparing transcriptomic sex-differences in ME/CFS are required in order to make more generalized conclusions about the disease.

And, that's fair enough, but I really want to know that the decision to focus on 20 particular women with ME/CFS was made before the women were recruited and the data was examined, and that they weren't a cherry-picked sample of a larger study. I find the concept of this study (proteomics and cell types before and after an exercise challenge) very good, and the results are very interesting. But, I don't like seeing these indications of possible bias.

 

[Ravn]

That raises questions in my mind - did they do this study with men also, but not include those results?

Could be this:
https://www.s4me.info/threads/sex-d...ilot-study-2023-nathanson-klimas-et-al.33738/

 

[SNT Gatchaman]

The methods section isn't at all reassuring (it's also not in the usual place, after the introduction, but tucked away after the discussion).

That seems increasingly common. The pattern of introduction, results, discussion, references <-> methods seems particularly common though not universal in molecular and immunology papers, eg Science. Nature articles seem to reduce introduction, results and discussion, and go with main, references, methods eg 1 and 2. The methods are often de-emphasised in a smaller font.

 

[Hutan]

That seems increasingly common.

Yes, although presumably it's still a choice. I just wonder if that structuring was used for a reason in this paper.

I haven't read any of these yet, but so far I found the following refs, mostly from the last 3 years, plus a few potentially related. Feel free to peel this off to a separate thread if there's interest.

Thanks SNT Gatchaman.

It's hard to know what is going on when they don't give us baseline concentrations.

CD8+ T cells

The tables suggest that CD8+ T cell numbers changed -13.444 fold from peak exercise (T1) to 4 hours after exercise (T2) in healthy controls. That's a huge decrease in the healthy controls - if the T1 value was 100, the T2 value would be 7. The tables present no figures for CD8+ cells in the ME/CFS participants, and no values for CD8+ cells at T0 for the healthy controls. Presumably that's because the only statistically significant change over time was that massive reduction from peak exercise to 4 hours afterwards in the healthy controls.

The paper suggests that this shows that people with ME/CFS aren't able to reduce inflammation after an exercise challenge.

By not properly reducing inflammation, ME/CFS patients have altered lymphocyte cell populations. Recent studies have found increased proportions of mucosal-associated invariant T cells, as well as effector CD8+ T cells in patients with ME/CFS [59]. Meanwhile, the proportions of CD8+ T cells were significantly decreased in HCs during the recovery period (Table 3). In order to recover from a physical stressor, HCs may be able to inactivate their immune cells and reduce inflammation, whereas these pathways are dysregulated in patients with ME/CFS leading to constant low-grade inflammation.

The problem is, this paper gives us no evidence for the levels of CD8+ T cells being higher at rest in people with ME/CFS, and it doesn't report any absolute values at any time. A straightforward table with the values at T0, T1 and T2 for the ME/CFS and healthy controls for each cell type would have been very useful. I think there could be important findings here, but the presentation isn't giving us solid data.

 

[Jonathan Edwards]

Perhaps the authors felt that the outcomes of thousands of concurrent measurements could not be fairly represented or even-handedly conveyed by only including a small selection of detailed specifics in as limited a space as an abstract or a conclusion. Seems reasonable to me if so.

But there aren't any specifics.
I have been reading abstracts of immunology papers for forty years. I am afraid this abstract gives the clear impression that it will be followed by muddled ideas and poor methodology.

A significant piece of scientific work produces some specific findings that can be itemised in an abstract, with figures that can give the reader an indication of likely relevance.