Cytokine signature associated with disease severity in chronic fatigue syndrome patients
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Cleare is hilarious. He is Wessely's colleague, no one in the SMC every can read apparently.
The data has implied that ME is multiple groups, and broadly defined CFS is highly heterogeneous, for a long time.
Agreed. We have yet to do that with this paper though. It does take a bit of time. My comment was more about the SMC comments, less about the paper. You cannot trust press releases, and abstracts are not complete enough to evaluate a paper. I will be working through the paper soon, and I am guessing many here have done that or are already doing it.
Nature:
https://www.nature.com/articles/d41586-017-02105-4
And one more UK media:
http://www.express.co.uk/life-style...igue-syndrome-me-symtoms-blood-test-diagnosis
No trace of the SMC's experts...
https://www.nature.com/articles/d41586-017-02105-4
And one more UK media:
http://www.express.co.uk/life-style...igue-syndrome-me-symtoms-blood-test-diagnosis
No trace of the SMC's experts...
I have only just started the paper but I wanted to comment on these two points.
The first is that this might well be the basis for a diagnostic test, but not the way people think. It would not be a test for ME/CFS. It would be a test for ME/CFS severity.
Second, nearly all psychiatric disease categories are made up and not proven. Nearly all. The diseases are real, the categories are artificial constructs that fit very poorly with reality. I fully agree with the person who wrote (on one of the links) that many diseases are really heterogeneous mergings of disease, with depression as an example. Depression is just a symptom, much like pain or fatigue. Its real, it can be extremely serious, but its not the disease. Its a symptom of a huge variety of diseases, all thrown in together. (Actually a huge range of similar symptoms.)
On the first point I think the paper potentially shows that ME may not be caused by inflammation, but that it modifies the inflammatory profile.
Now, back to that paper.
The first is that this might well be the basis for a diagnostic test, but not the way people think. It would not be a test for ME/CFS. It would be a test for ME/CFS severity.
Second, nearly all psychiatric disease categories are made up and not proven. Nearly all. The diseases are real, the categories are artificial constructs that fit very poorly with reality. I fully agree with the person who wrote (on one of the links) that many diseases are really heterogeneous mergings of disease, with depression as an example. Depression is just a symptom, much like pain or fatigue. Its real, it can be extremely serious, but its not the disease. Its a symptom of a huge variety of diseases, all thrown in together. (Actually a huge range of similar symptoms.)
On the first point I think the paper potentially shows that ME may not be caused by inflammation, but that it modifies the inflammatory profile.
Now, back to that paper.
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Yes, we lack replication of many findings. It throws them all in doubt.
Mast cells release TGF-beta. (A Pubmed search on 'transforming growth factor and mast cells' yields 500 studies.)
Why is there so little interest in mast cells, especially considering how many ME patients have mast cell problems?
Why is there so little interest in mast cells, especially considering how many ME patients have mast cell problems?
I agree. Without a hypotheses to test, how are they going to find a cause? It seems like testing a good hypotheses is the best way to get to the cause. I feel like the researchers continue to look for bio-markers, when we really need to know the root cause.
If they found the root cause, it could be much easier to find bio-markers, because they would have a better understanding of the disease pathology to follow and find bio-markers.
Jim
If they found the root cause, it could be much easier to find bio-markers, because they would have a better understanding of the disease pathology to follow and find bio-markers.
Jim
I don't understand the headline in the Telegraph. They say cytokines correlate with CFS severity. It means the severe CFS cases tend to have higher levels of some pro-inflammatory cytokines than those with mild CFS.
BUT: The study also says, cytokines (except two) overall don't differ between CFS patients and healthy people. So how could a lab test tell you if you have CFS or not?
Do severe CFS cases have significantly higher levels of these cytokines than healthy controls? Or is there just no difference on average, including severe, moderate and mild cases?
Sorry for asking, I know the study is published and I could read it myself, but my experience in understanding and interpreting medical studies is very limited.
BUT: The study also says, cytokines (except two) overall don't differ between CFS patients and healthy people. So how could a lab test tell you if you have CFS or not?
Do severe CFS cases have significantly higher levels of these cytokines than healthy controls? Or is there just no difference on average, including severe, moderate and mild cases?
Sorry for asking, I know the study is published and I could read it myself, but my experience in understanding and interpreting medical studies is very limited.
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Subsets indeed. Wessely's disciples will just manipulate this and enhance it with a PACE criteria follow up study. Ignore this though, pathogen studies that bind to Montoya's findings are where it's at.
If I recall correctly, this data (or similar narrative of it) is around 3 years 3 months old from what would have been a game changing publication but was blocked by government in America as the people involved in infecting us all wanted Dr Lipkin/Dr Hornig's paper promoted FIRST, meaning Dr Montoya's was halted. If so, this allowed 'no inflammation' to be the narrative of post XMRV 'we believe you CFS so lets call it ME/CFS' to allow for the bizarre concept of SEID (as organic CFS) to be completed early, and declare there is no inflammation in CFS, and thus inflammation cannot be part of the word SEID - thus nullifying the resurgence in ME and interest in retroviruses as the diagnostic criteria of SEID would never focus on the subset of patients with ME within SEID. Clever, huh?! The old CFS trick again. Notice SEID was nothing like ME either, although battered down CFS patients thought SEID was a great improvement, as they would, not understanding why it appeared at the time it did and dismissing the fact all ME experts were banned from formulating it, rather like banning endocrinologists to devise a set of criteria to diagnose Acromegaly as they too might be 'biased'.
Meaning? The high cytokine inflammation patients in this study of Dr Montoya's are likely those with pathogenic HERV retroviruses which KDM is finding in his ME patients too, patients who allegedly have a new variant of bacteria that evades the immune system leading to many types on infections in ME that are otherwise hidden (needs deep sequencing).
My results are identical to those shown although I did mine in bits, as I didn't have my own lab to perform 17 cytokine assays simultaneously! In contrast, Dr Lipkin/Dr Hornig no inflammation after 3 years study, the patients don't have retroviruses, and allegedly none were found in Dr Bateman's samples either, only Dr Montoya's inflammation based CFS subset. This is of no surprise when CDC are telling people, via CFS, they all have the same illness without running any tests first (Fukuda CFS) to confirm this. We'll all have different reasons for being unwell obviously.
Of interest to me is Scientists replicating my own blood work.The cancer retroviruses and other hybrid Frankenstein infections now in the human population can cause elevations in VEGF and TGF-b1, and really no other explanation can be given in the absence of hypoxia, uncontrolled asthma, certain infections, or vascular disease. Lab mice with human activated retroviruses and brain disease share the same cytokine signatures as humans with CFS and brain illness who were false 'XMRV' positive - redflag.
It now makes sense the only reason the CFS patients aren't dead is they fail to die from a massive inflammatory response seen in conditions like Lupus (that can kill you) is their B cells are impaired and growing the wrong form. They likely aren't correct functioning mature B Cells. In addition the HERV retroviruses are likely integrated into 'hot spots' and affect how the B Cells produce antibodies ironically saving you from far worse disease. This is likely why the British forbid PVFS patients to donate bone marrow after death, and ME CFS when alive. UK females cannot donate umbilical cord for the same reason. The state know we're all infected since the 1990's but only in 2011 did they discover they're air-borne in cancer research lab workers who didn't take precautions when working with mice, inhaled them in the lab, and spread them to close contact family members which is why they agreed to Cerus Intercept technology cleaning up the blood for retroviruses they told the public don't exist.
When scientists find growth factors elevated like TGF-b1, VEGF with the caveats I gave, at the best they government cronies will push them out the way, screen 'CFS' patients for cancer, and then come to a halt and shrug. I don't stop though and keep going. None of us should except no for an answer and we'll get there eventually, albeit hanging onto our respective cliffs by one last fingernail.
For people interested, although expensive, you can test for Cytokines and TGF-b1, VEGF, Leptin in commercial labs. Make sure you spin and freeze the samples if required, as Cytokines are incredibly bad to mail in the post and won't last to give you an accurate result. VEGF is fine though.
If I recall correctly, this data (or similar narrative of it) is around 3 years 3 months old from what would have been a game changing publication but was blocked by government in America as the people involved in infecting us all wanted Dr Lipkin/Dr Hornig's paper promoted FIRST, meaning Dr Montoya's was halted. If so, this allowed 'no inflammation' to be the narrative of post XMRV 'we believe you CFS so lets call it ME/CFS' to allow for the bizarre concept of SEID (as organic CFS) to be completed early, and declare there is no inflammation in CFS, and thus inflammation cannot be part of the word SEID - thus nullifying the resurgence in ME and interest in retroviruses as the diagnostic criteria of SEID would never focus on the subset of patients with ME within SEID. Clever, huh?! The old CFS trick again. Notice SEID was nothing like ME either, although battered down CFS patients thought SEID was a great improvement, as they would, not understanding why it appeared at the time it did and dismissing the fact all ME experts were banned from formulating it, rather like banning endocrinologists to devise a set of criteria to diagnose Acromegaly as they too might be 'biased'.
Meaning? The high cytokine inflammation patients in this study of Dr Montoya's are likely those with pathogenic HERV retroviruses which KDM is finding in his ME patients too, patients who allegedly have a new variant of bacteria that evades the immune system leading to many types on infections in ME that are otherwise hidden (needs deep sequencing).
My results are identical to those shown although I did mine in bits, as I didn't have my own lab to perform 17 cytokine assays simultaneously! In contrast, Dr Lipkin/Dr Hornig no inflammation after 3 years study, the patients don't have retroviruses, and allegedly none were found in Dr Bateman's samples either, only Dr Montoya's inflammation based CFS subset. This is of no surprise when CDC are telling people, via CFS, they all have the same illness without running any tests first (Fukuda CFS) to confirm this. We'll all have different reasons for being unwell obviously.
Of interest to me is Scientists replicating my own blood work.The cancer retroviruses and other hybrid Frankenstein infections now in the human population can cause elevations in VEGF and TGF-b1, and really no other explanation can be given in the absence of hypoxia, uncontrolled asthma, certain infections, or vascular disease. Lab mice with human activated retroviruses and brain disease share the same cytokine signatures as humans with CFS and brain illness who were false 'XMRV' positive - redflag.
It now makes sense the only reason the CFS patients aren't dead is they fail to die from a massive inflammatory response seen in conditions like Lupus (that can kill you) is their B cells are impaired and growing the wrong form. They likely aren't correct functioning mature B Cells. In addition the HERV retroviruses are likely integrated into 'hot spots' and affect how the B Cells produce antibodies ironically saving you from far worse disease. This is likely why the British forbid PVFS patients to donate bone marrow after death, and ME CFS when alive. UK females cannot donate umbilical cord for the same reason. The state know we're all infected since the 1990's but only in 2011 did they discover they're air-borne in cancer research lab workers who didn't take precautions when working with mice, inhaled them in the lab, and spread them to close contact family members which is why they agreed to Cerus Intercept technology cleaning up the blood for retroviruses they told the public don't exist.
When scientists find growth factors elevated like TGF-b1, VEGF with the caveats I gave, at the best they government cronies will push them out the way, screen 'CFS' patients for cancer, and then come to a halt and shrug. I don't stop though and keep going. None of us should except no for an answer and we'll get there eventually, albeit hanging onto our respective cliffs by one last fingernail.
For people interested, although expensive, you can test for Cytokines and TGF-b1, VEGF, Leptin in commercial labs. Make sure you spin and freeze the samples if required, as Cytokines are incredibly bad to mail in the post and won't last to give you an accurate result. VEGF is fine though.
@Wonkmonk I thought the same. How would a test work if there is no difference to healthy controls. But assumed I must be missing something as people seemed excited and these are scientists who must know what they are doing and have thought of that. But reading above I now see that depression gives similar or worse results. So I am confused by the excitement. Did the team at Stanford not know this?
I might be being oversimplistic, but in a large-ish study like this I don't understand why the groups are split into a testing/analysis cohort and a validation cohort. Surely you increase your statistical power if you look at, say, 70% of the data, find those variables that appear significant (still correcting for multiple comparisons), then look solely at those variables in the validation cohort to see whether the same correlation is seen?
(I'll admit it's been a good few years since I did statistics, and even then it was 'Statistics for Engineers' so I might be getting that bit wrong).
(I'll admit it's been a good few years since I did statistics, and even then it was 'Statistics for Engineers' so I might be getting that bit wrong).
If we assume none of the participants of Dr Montoya's study was clinically depressed, wouldn't it still be interesting that CFS patients have some of the same distinctive metabolic test results you can find in depression?
I wouldn't say the fact that depressed people might have similar cytokine profiles makes Montoya's study less valuable.
I wouldn't say the fact that depressed people might have similar cytokine profiles makes Montoya's study less valuable.
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Love how a veterinarian cover it here...she did a great job.
I haven't studied the paper in detail, but I think it may be that the mean cytokines levels were not significantly different from controls. This is similar to the Lipkin et al. paper, where the overall difference between the mean cytokines levels of all patients and controls were not strongly different statistically [ However, 7 of those 51 cytokines were p>0.05, 2 were p>0.01. All but one of those nine cytokines (Leptin) were lower than controls].
Here, it's when you break the patients into subgroups of mild, moderate, and severe that the significant statistical differences show up.
I think the ultimate idea may not be that they check your cytokine levels and then tell you whether you're mild, moderate or severe. Rather, you tell them, by test and/or personal report whether you are mild, moderate or severe. Then they look at your cytokine profile and, if it matches, you're judged to have ME/CFS. If it doesn't, you may have something else.
If that were true, the problem would seem to be restricted to verifying the moderate cases, which, apparently, would have cytokine profiles similar to controls.
Here, it's when you break the patients into subgroups of mild, moderate, and severe that the significant statistical differences show up.
I think the ultimate idea may not be that they check your cytokine levels and then tell you whether you're mild, moderate or severe. Rather, you tell them, by test and/or personal report whether you are mild, moderate or severe. Then they look at your cytokine profile and, if it matches, you're judged to have ME/CFS. If it doesn't, you may have something else.
If that were true, the problem would seem to be restricted to verifying the moderate cases, which, apparently, would have cytokine profiles similar to controls.
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Thanks for reminding me. Here's the title and conclusion of the previous study (by researchers in Australia):
Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study
Conclusion
Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.
I couldn't figure how they came to look at activin but your post highlights a link i.e. they are part of the TGF-beta superfamily.
As snow leopard says "It's the sixth study so far and the only consistent cytokine finding. I don't much care for these cytokine studies, but I'm starting to pay more attention to TGF-β!"
Maybe we should start paying more attention to the above activin Australian study and replication of same.
Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study
Conclusion
Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.
I couldn't figure how they came to look at activin but your post highlights a link i.e. they are part of the TGF-beta superfamily.
As snow leopard says "It's the sixth study so far and the only consistent cytokine finding. I don't much care for these cytokine studies, but I'm starting to pay more attention to TGF-β!"
Maybe we should start paying more attention to the above activin Australian study and replication of same.
Sorry, maybe I'm blind -- can you guys see anything on how they judged severity?
[Edit: nm, it's the MFI.]
[Edit: nm, it's the MFI.]
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