Here is a link to the
paper which I haven't read.
Looks like three key sets of findings here:
- Dr. Hanson and her colleagues did not see significant differences in mitochondrial respiration, the cell’s primary energy-producing method, between healthy and ME/CFS cells at rest or after activation. However, results suggest that glycolysis, a less efficient method of energy production, may be disrupted in ME/CFS. Compared to healthy cells, CD4 and CD8 cells from people with ME/CFS had decreased levels of glycolysis at rest. In addition, ME/CFS CD8 cells had lower levels of glycolysis after activation.
- Dr. Hanson’s group also looked at mitochondrial size and membrane potential, which can indicate the health of T cell mitochondria. CD4 cells from healthy controls and people with ME/CFS showed no significant differences in mitochondrial size nor function. CD8 cells from people with ME/CFS showed decreased membrane potential compared to healthy cells during both resting and activated states.
- Dr. Hanson’s team examined associations between cytokines, chemical messengers that send instructions from one cell to another, and T cell metabolism. The findings revealed different, and often opposite, patterns between healthy and ME/CFS cells, suggesting changes in the immune system. In addition, the presence of cytokines that cause inflammation unexpectedly correlated with decreased metabolism in T cells.
So it's not the amount of T cells being made (which would be found in a CBC/Differential) or their clonal character (Mark Davis's idea) but rather the metabolic behaviors/requirements of the cells, whether activated or latent (if that's the right word). I'm not sure what the decreased membrane potential means in conjunction with the finding of normal mitochondrial size and function. Maybe the mitochondria appear fine when examined in isolation, but within the cellular milieu they are behaving strangely? Membrane potential would be an electrical property, I wonder how it's measured and if it could be done using a nanoneedle type of device.
The last thing about cytokines is interesting as well. Rather than showing a correlation with patient symptoms/severity, there is a correlation shown with another hard quantitative measure, the T-cell metabolic dysfunction.
I wonder what the follow-up to this would entail. I feel as though we are in the period of ME/CFS research in which scientists are finding obviously measurable stuff by digging a little bit deeper than previous tests would have shown, but the next steps will be harder in terms of how to tease out the causal factors.
Edit: Just skimmed the paper, especially focusing on the discussion section at the end. Found this paragraph at the end to be rather interesting:
It is clear that the immune systemplays a role in ME/CFS. Our data indicate that there are existing reductions in resting T cell metabolism inpatients. In particular,CD8+ T cells have altered mitochondrial membrane potential and an impairment in their metabolic response to activation. Both CD4+ and CD8+ T cells have significant reductions in glycolysis. This hypometabolism in T cells aligns with other findings of hypometabolism in ME/CFScells(50, 51, 59). Furthermore, ME/CFS patients appear to have altered relationships between plasma cytokine abundance and T cell metabolism, where proinflammatory cytokines unexpectedly correlate with hypometabolism. Such a dysregulation may indicate that ME/CFS T cells have lost responsiveness to some proinflammatory cytokines. Along with hypometabolismin immune cells, thisis consistent with a possible ongoing infection (42), though such an agent has not yet been identified. A high priority moving forward will be determiningthe mechanism behind hypometabolism in ME/CFS T cells, as well as howaltered metabolism affectsthe function of these cells.
Would love to have some follow-up here because it seems like almost nobody (not even Ron Davis, exactly) is willing to totally dispense with the idea that ongoing infections play a role in ME/CFS. I would like to know whether the experts think the pathogen is the issue or that something to do with our immune-metabolic response to a common pathogen carried by healthy people is the real issue.