ME/CFS patients exhibit altered T cell metabolism and cytokine associations (2019) Mandarano, Hanson et al

Ron · Dec 12, 2019

https://www.nih.gov/news-events/news-releases/study-finds-differences-energy-use-immune-cells-me/cfs

New findings published in the Journal of Clinical Investigation suggest that specific immune T cells from people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) show disruptions in the way they produce energy. The research was supported by the National Institutes of Health.

“This research gives us additional evidence for the role of the immune system in ME/CFS and may provide important clues to help us understand the mechanisms underlying this devastating disease,” said Vicky Whittemore, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which partially funded the study.

Kalliope · Dec 12, 2019

https://twitter.com/user/status/1205178097399717888

https://twitter.com/user/status/1205183418062929920

Andy · Dec 12, 2019

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease with no known cause or mechanism. There is an increasing appreciation for the role of immune and metabolic dysfunction in the disease. ME/CFS has historically presented in outbreaks, often has a flu-like onset, and results in inflammatory symptoms. Patients suffer from severe fatigue and post-exertional malaise. There is little known about the metabolism of specific immune cells in ME/CFS patients.

To investigate immune metabolism in ME/CFS, we isolated CD4+ and CD8+ T cells from 53 ME/CFS patients and 45 healthy controls. We analyzed glycolysis and mitochondrial respiration in resting and activated T cells, along with markers related to cellular metabolism, and plasma cytokines. We found that ME/CFS CD8+ T cells have reduced mitochondrial membrane potential compared to healthy controls. Both CD4+ and CD8+ T cells from ME/CFS patients had reduced glycolysis at rest, while CD8+ T cells also had reduced glycolysis following activation. ME/CFS patients had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from healthy control subjects. Our data indicate that patients have impaired T cell metabolism consistent with ongoing immune alterations in ME/CFS that may illuminate the mechanism behind this disease.
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Open access, https://www.jci.org/articles/view/132185

John Mac · Dec 12, 2019

Talk given on this paper is now on Youtube

https://www.youtube.com/watch?v=4jBKt-1ULFg

Jaybee00 · Dec 12, 2019

Ok but how does this altered T cell metabolism affect brain stem function as shown in other research?

Hoopoe · Dec 12, 2019

I suspect the so far few responses to this are due to this being a very technical paper, packed with information and findings.

Our data indicate that there are existing reductions in resting T cell metabolism in patients. 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/CFS cells(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, this is consistent with a possible ongoing infection (42), though such an agent has not yet been identified. A high priority moving forward will be determining the mechanism behind hypometabolism in ME/CFS T cells, as well as howaltered metabolism affects the function of these cells.
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Forbin · Dec 12, 2019

From the video:

So again, we're seeing these opposite associations to what we would expect in ME/CFS patients and this suggests an overall dysregulation in cytokine and metabolism connections in patients

So to take this back to the big picture, if we look at our spectrum of different metabolic states and disease states, everything that we and others are seeing in cells is suggestive of hypometabolism in ME/CFS cells and this would be consistent with some kind of ongoing chronic infection - as would these dysregulations we're seeing in our cytokine associations, but we obviously have a lot more work to do to determine if this is the case.
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DigitalDrifter · Dec 13, 2019

What was that Wessely said about a little less t-cells and a little more psychology?

beverlyhills · Dec 13, 2019

Is Maureen Hanson a member of this board?

Why wouldn't sedentary individuals have reduced glycolysis in their T-cells?

Ambulatory individuals would have higher creatine kinase, which in turn improve T-cell function, and that is just one pathway, there are dozens more that explain this.

And how is this finding helpful, if I explained it one sentence.

Sly Saint · Dec 13, 2019

article
ME and Chronic Fatigue Syndrome Linked to Immune Cell Changes

New findings published in the Journal of Clinical Investigation suggest that specific immune T cells from people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) show disruptions in the way they produce energy. The research was supported by the National Institutes of Health.

“This research gives us additional evidence for the role of the immune system in ME/CFS and may provide important clues to help us understand the mechanisms underlying this devastating disease,” said Vicky Whittemore, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which partially funded the study.
Click to expand...

“Our work demonstrates the importance of looking at particular types of immune cells that have different jobs to do, rather than looking at them all mixed together, which can hide problems specific to particular cells,” said Dr. Hanson. “Additional studies focusing on specific cell types will be important to unravel what’s gone wrong with immune defenses in ME/CFS.”
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https://www.technologynetworks.com/...syndrome-linked-to-immune-cell-changes-328427

Pondering · Dec 13, 2019

this would be consistent with some kind of ongoing chronic infection.
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Is it though? So many people have looked for this and found anything. I am wondering if there is not some other mechanism at work. Look at the recent finding that measles has a long term impact on the immune system. Recent research seems to be providing the idea that the virus might not need to still be there.

rvallee · Dec 13, 2019

DigitalDrifter said: ↑

What was that Wessely said about a little less t-cells and a little more psychology?
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Always a good rule of thumb to do the opposite of what he thinks is a good idea. Holds up perfectly so far.

Badpack · Dec 13, 2019

"We found that ME/CFS CD8+ T cells have reduced mitochondrial membrane potential compared to healthy controls."

That even further makes me want to finally try out elamipretide.

ScottTriGuy · Dec 13, 2019

Badpack said: ↑

...elamipretide
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Sounds like you've been following its development - did they publish the phase 3 results?

Badpack · Dec 13, 2019

@ScottTriGuy Data collection ends this year. Early next year is the meeting they said for a possible publication. With Alexion they also found a distributor. Seems like a possible 2020 availability.

Ravn · Dec 14, 2019

John Mac said: ↑

Talk given on this paper is now on Youtube

https://www.youtube.com/watch?v=4jBKt-1ULFg

Click to expand...

The video is really good. I recommend watching it before trying to digest the paper itself, which is rather technical.

What I'm still trying to get my head around is this. On the one hand they say:

We compared cytokine abundances between ME/CFS patients and healthy controls. We did not find significant differences between ME/CFS patient and healthy control subjects for any of the 44 cytokines detected
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On the other hand they find:

However, we did observe a number of significant correlations between plasma cytokines and metabolism. Most interestingly, these correlations were unique in ME/CFS patients compared to the control group.
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So if the cytokines are the same in ME and HC but there are different correlations between cytokines and metabolism it has to be the metabolism that's skewed? And because the metabolism is skewed even normal levels of cytokines have weird effects? Or have I got that completely wrong?

fds · Dec 14, 2019

John Mac said: ↑

Talk given on this paper is now on Youtube

https://www.youtube.com/watch?v=4jBKt-1ULFg

Click to expand...

I thought this was a good presentation and as @Ravn said above it does help with understanding the paper

lansbergen · Dec 14, 2019

https://www.immunology.org/public-information/bitesized-immunology/cells/cd8-t-cells

CD8+ T Cells

Sly Saint · Dec 14, 2019

another article
Study finds differences in energy use by immune cells in ME/CFS

New findings published in the Journal of Clinical Investigation suggest that specific immune T cells from people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) show disruptions in the way they produce energy. The research was supported by the National Institutes of Health.

“This research gives us additional evidence for the role of the immune system in ME/CFS and may provide important clues to help us understand the mechanisms underlying this devastating disease,” said Vicky Whittemore, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which partially funded the study.
Click to expand...

https://www.mlo-online.com/molecula...rences-in-energy-use-by-immune-cells-in-mecfs

lansbergen · Dec 14, 2019

Maybe clues can be found in the TSE literature.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149501/

However, these CD4 and CD8 T cells are defective in such an effector function(s) as IFN-γ and TNF-α expression or release or lytic activity.

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