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Jarred Younger on CFS subgroups (video)

Never Give Up

Collecting improvements, until there's a cure.
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971
Says that preliminary analysis of tracking metabolites for 25 consecutive days in the same patient seems to be revealing subtypes.

In about 1/3 of the patients fatigue correlates with rising and falling C reactive protein, which indicates an ongoing infection of some sort.

In about another third, fatigue tracks with fractalkines, which indicates a malfunctioning immune system.

ETA: I wonder if they tracked anything other than "fatigue".
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
The substance of the video is really interesting and makes sense

Some thoughts

- what are the p values of CRP and fracktlekine correlation with fatigue? Are these patterns meaningful or is it attractive noise? We will likely find out when he publishes

- if the pathogen of the CRP subgroup is in tissue or is yet to be discovered it won't show up in his daily blood draws. Shotgun metagenomics could solve the second issue, but you can't really do a stomach or muscle biopsy on someone every day for 25 days

- the dataset is small so this is very preliminary (~8 per subgroup), but subsequent cohorts will hopefully bare this out

- are these analytes causative and/or could suppressing them be ameriolative of symptoms? are these the blood borne factors that Ron Davis has found to make cells abnormal? Or are they bystanders or collaborators with something else?

- and of course, what to make of the other 3rd with no correlation yet discovered
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
More on fractalkine, not surprisingly it's related to microglial cells

Fractalkine is found commonly throughout the brain, particularly in neural cells, and its receptor is known to be present on microglial cells. It has also been found to be essential for microglial cell migration.[7] CX3CL1 is also up-regulated in the hippocampus during a brief temporal window following spatial learning, the purpose of which may be to regulate glutamate-mediated neurotransmission tone. This indicates a possible role for the chemokine in the protective plasticity process of synaptic scaling.[8]
 
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15,786
Also of interest is that the fluctuating CRP values aren't necessarily elevated out of a normal range at any point. He proposes that this could be due to a low-level biological infection and/or an infection trying to emerge.

More specifically with regards to fractalkine, he says it's elevated in a lot of autoimmune and chronic inflammatory disorders where there isn't an infection.

He's still analyzing the group which has neither the CRP nor the fractalkine tracking with their fatigue symptoms, to look for identifying characteristics. Their symptoms might be related to different immune markers, or driven by energy metabolism, endocrine disregulation, etc, instead of the immune system.

He's just started digging into this data, and is definitely going to follow up on it. He hopes they can develop some objective tests to distinguish between subtypes to use more targeted treatments.

For the CRP group, they need to start looking for viruses and bacteria, and any fluctuations of those.

They're starting with a large new cohort to see if these results replicate.

He can't give more information, due to upcoming publication in a scientific journal. But he'll continue giving us updates with little peeks into what's going on.
 

Kati

Patient in training
Messages
5,497
Also of interest is that the fluctuating CRP values aren't necessarily elevated out of a normal range at any point. He proposes that this could be due to a low-level biological infection and/or an infection trying to emerge.

More specifically with regards to fractalkine, he says it's elevated in a lot of autoimmune and chronic inflammatory disorders where there isn't an infection.

He's still analyzing the group which has neither the CRP nor the fractalkine tracking with their fatigue symptoms, to look for identifying characteristics. Their symptoms might be related to different immune markers, or driven by energy metabolism, endocrine disregulation, etc, instead of the immune system.

He's just started digging into this data, and is definitely going to follow up on it. He hopes they can develop some objective tests to distinguish between subtypes to use more targeted treatments.

For the CRP group, they need to start looking for viruses and bacteria, and any fluctuations of those.

They're starting with a large new cohort to see if these results replicate.

He can't give more information, due to upcoming publication in a scientific journal. But he'll continue giving us updates with little peeks into what's going on.

We are so lucky to have Jarred as researcher for ME and FM. He is highly intelligent and i am not sure if it's luck or hard work or both, but he has definitely risen and built a strong team at UAB, from scratch.

Looking forward to the paper, and the next ones after that. Also thankful he is willing to collaborate with Dr Davis and others. Great minds all together can litterally make miracles.
 
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1,478
It does give you hope doesn't it? It is interesting that "third" of the population seems to be cropping up again and again.

It does make you wonder what third you are in doesn't it? I wonder whether onset of symptoms could be linked to subtype in a more detailed way once we know more.

Does anyone know when he plans to publish?
 

Londinium

Senior Member
Messages
178
- what are the p values of CRP and fracktlekine correlation with fatigue? Are these patterns meaningful or is it attractive noise? We will likely find out when he publishes

Lol, I'm glad I'm not the only person who watched it and immediately went 'I wonder what the p value is?' ;) I can't wait for the paper to come out to also see what the r values are for the CRP/fractalkine subgroups as a whole. The data presented looks like a pretty high correlation coefficient to my untrained eye, but it'll be interesting to know if they are the ones selected because they show the correlation best or whether they are representative of the subgroup as a whole.

I'm naturally cautious when findings apply to subgroups and are based on a lot of variables being tested - especially due to funding limitations on ME/CFS research meaning cohort sizes are small. It's encouraging to hear the team are replicating in a wider cohort - if they stick to looking at CRP and fractalkine only that should provide a lot more statistical power.

More on fractalkine, not surprisingly it's related to microglial cells

This paper provides some interesting titbits as well. My brain is still a touch fried as I'm recovering from a relapse but one of the things that jumped out was the way it causes white blood cells to attach to endothelial cells. I'm making a massively speculative leap but could this explain some of the endothelial dysfunction seen in some ME/CFS patients?