Jarred Younger on CFS subgroups (video)

[Jonathan Edwards]

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".

I cannot access the video at present so can only go on the comments. Raised C R P is not specific for infection. It is a standard response to small immune complexes in autoimmunity as well.

 

[halcyon]

I cannot access the video at present so can only go on the comments. Raised C R P is not specific for infection. It is a standard response to small immune complexes in autoimmunity as well.

And it seems like fractalkine release can be induced by cytokines normally associated with infection, so it seems like his subgroup demarcation may not be so clean.

 

[Valentijn]

It does make you wonder what third you are in doesn't it?

My CRP was raised a couple times when tested, so maybe indicating infection. I don't think it's been tested since Lyme & Bartonella treatment though.

Raised C R P is not specific for infection. It is a standard response to small immune complexes in autoimmunity as well.

Does it usually fluctuate in synch with fatigue or other symptoms in RA or other autoimmune patients? Or is this a pretty novel thing for Dr. Younger to be tracking in any patients?

 

[Murph]

1. I love this kind of video. Results within days of the experiments being done!! This is the new frontier of science - all researchers should do it like this!! The fact he can give us what seems like a lot and still save enough for publication is amazing. I respect him being honest about the fact he's not giving us the whole picture because of the need to publish.And it is not just good for us - it is good for other researchers.

2. The question of subgroups is always interesting. I'd guess the patient charts he showed were the cleanest clearest examples of each subgroup. There must be edge cases that reduce the tightness of the correlation and were candidates for being chucked in bin number 3. I hope the final paper shows all the participants data not just the means, so we can judge whether the subgroups are truly distinct.

3. The question of the accuracy of the subgroups is especially the case since he is tracking many candidate substances in the blood. If you look at enough analytes, you will find a spurious correlation in at least one due to random chance. So the existence of the groups hypothesised will have to depend on validation.

4. From what I see, Fractalkines are also associated with T cells and endothelial cells (albeit, I admit, reading the wikipedia hasn't enlightened me on the nature of that association...!) https://en.wikipedia.org/wiki/CX3CL1

"...Soluble CX3CL1 potently chemoattracts T cells and monocytes, while the cell-bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells, where it is primarily expressed..."

 

[Murph]

I had not seen this earlier video from him

It contains a very interesting result about leptin and some info on a study he intends to do in the very severe.

Also, in this video he announces that his staff have bought him a special light for making videos, and indeed he is softly lit and looks good. Perhaps the globe blinked out though, because in the video posted to start this thread he's back to having the room light on and looking a trifle shiny!

 

[temple88]

I was in the first cohort of this study and cannot for the life of me remember the questions I had to answer every day. We had a tablet sent home with us and every morning and every night had to answer a series of questions about how we were feeling. I think there were questions about more than just fatigue but maybe someone who was in it more recently can answer. I participated two years ago.

 

[trishrhymes]

I cannot access the video at present so can only go on the comments. Raised C R P is not specific for infection. It is a standard response to small immune complexes in autoimmunity as well.

Is this any better, @Jonathan Edwards ?

 

[A.B.]

This study seems to confirm that we really need more longitudinal studies.

 

[Mij]

My CRP has been tested several times over the years but was never elevated.

 

[Marco]

Two points.

He notes that while CRP levels 'track' self-reported fatigue they're within a range usually considered 'normal'. Similar to Younger's earlier findings on leptin which tracked fatigue levels but were within normal physiologic range. That strikes me as an important clue. I'd be interested to know if fractalkine levels were similar.

Secondly, and I've only watched the video once and could be mistaken, but it seems to me from the graphs presented that, while tracking fatigue, the immune parameters, whether CRP or fractalkine, LAG the change in self reported fatigue which suggests to me a third party or parties.

 

[Kati]

My CRP has been tested several times over the years but was never elevated.

Mine is on the elevated side, but not high enough to be in the rheumatologic side. High enough to put me in the moderate cardiac risk.

Dr Younger made mention that the values were within range but fluctuating with reports of fatigue.

What puzzles me is how people have such fluctuations in their fatigue from day to day. For me every day is a bad day, like groundhog day. Going out does not mean it's a good day, it means there is a high probablity I will be curled up in a ball when I get back home.

This said I am very thankful that he does this kind of work, much needed. I wish other teams did it too. Same for fibromyalgia.

 

[voner]

I had not seen this earlier video from him

It contains a very interesting result about leptin and some info on a study he intends to do in the very severe.

Also, in this video he announces that his staff have bought him a special light for making videos, and indeed he is softly lit and looks good. Perhaps the globe blinked out though, because in the video posted to start this thread he's back to having the room light on and looking a trifle shiny!

@Murph, thanks for posting that video.

pretty darn interesting. he says " clearly inflammation is playing a big role in these symptoms" and that right now by combining inflammatory markers and sex hormones ( estradiol, progesterone, testosterone) he can track/predict pain and fatigue variation in 80% of his ME/CFS and fibromyalgia patients he studied, which tracks "good days and bad days". he thinks by adding a couple other markers he'll get that to 90%.

it is so satisfying and encouraging to know that there are researchers who are also good communicators out there, like Dr Jared Younger.....

 

[edawg81]

The infection question... My illness sure 'feels' like a neurological infection.

It is something I wish would be investigated more. Thank you Dr. Younger for looking into this and the mid study update.

There are only two researchers that are looking for small infections outside the blood and CSF. Those are the radio labeled antibodies studies that Michael VanElzakker‏ and Jarred Younger are planning. That will hopefully shed light on a part of the immune disfunction that is still unknown, the CRP results seem (maybe?) indicative of this. A lot of us have elevated antibodies to numerous infections, but are PCR negative, what are those antibodies doing and where are they going? I hope that this research can be fast tracked. I am very excited what these studies are finding. Thank you for posting this video.

 

[Sushi]

Wow! He is hiring a phlebotomist to go to the homes of bedbound patients because they are so poorly studied. This guy is a bomb!

 

[rosie26]

Thanks so much Dr Younger. It's going to be so interesting to see all the subgroups and what is happening in each one.

I had my CRP tested at severe onset, it was normal. I feel like I have LPS involvement but I didn't know that CRP levels would automatically (?) be raised if that was the case.

 

[heapsreal]

He mentions the CRP is mostly within normal range but they can see with it rising up and down in correlation with symptoms. Im guessing from other testing that they say its infection related. He stated they werent releasing all the information due to copyrights and patents??

I recall previous research abouy good day, bad day study where leptin was tested and correlated with symptoms, i think this was Younger??

 

[trishrhymes]

I wonder whether he is also getting them to wear actometers. Tracking activity as well as symptoms could be really useful in this sort of study.

 

[Kati]

He stated they werent releasing all the information due to copyrights and patents??

He can't say everything because the paper has not been published- so this was a brief update, not the whole thing.

 

[alex3619]

He notes that while CRP levels 'track' self-reported fatigue they're within a range usually considered 'normal'.

What he appears to be looking for are symptom correlates. Such things are often not causal. However if you can find several that correlate with symptoms you can then identify targets to do further testing on, focusing on anything that can modify all or most of the substances that correlate with symptoms.

Normal CRP levels do not necessarily mean they do not correlate with symptoms.

An analogy I like to use is that obesity may have some correlation with tooth decay. Yet obesity does not cause tooth decay nor vice versa.

 

[alex3619]

What puzzles me is how people have such fluctuations in their fatigue from day to day.

This does need further explanation, but for that we may have to wait for the paper.

My guess is that there is a numerical fatigue score that is just a summation of individual answers with numerical values assigned. Such a score is just a clue ... it has no real value aside from indicating what factors being tracked might be interesting to study further.