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Immune network analysis of cerebrospinal fluid in ME/CFS with atypical & classical presentations

voner

Senior Member
Messages
592
it should be noted that in the discussion section Dr. Hornig and associates say,

The observation that our cohort included subjects with an A-ME/CFS profile who subsequently received a cancer diagnosis suggests that finding this profile should prompt a search for cancer, just as it does in paraneoplastic syndromes.

A-ME/CFS= atypical ME/CFS
 

Murph

:)
Messages
1,799
This table of results is interesting:
Screen Shot 2017-04-05 at 10.07.26 AM.png


What it seems to show is almost definitional. There are many differences in the early stages between typical onset ME/CFS and atypical, but they tend to converge.

You can observe that by the number of bolded p values in the second comparison column: 18. That column compares classical onset and atypical onset patients who've only had the disease a short time. A lot of differences!

But in the second last column (which compares long-duration patients who had classical vs atypical onsets) we see only three cytokines of 55 with statistically significant differences. Much more similar.

So over time, the differences between atypical and classical are decreasing. Which matches what I observe on this forum. People complain about different things, but there are few or no obvious links between what our problems are and how we got the disease

One obvious difference in the table is IL17A, which I highlighted. It has some seriously low p values and seems to consistently show difference over time between classical and atypical. I'd like to know more about what it does!

The conclusion says the overall level of cytokines is lower in atypical than classical, (although without a healthy control group I'm not sure whether that implies the atypical folk have depressed immune systems or the classical ones do?)

"Although few differences were apparent in cytokine levels across the different subsets within the A-ME/CFS subgroup, the atypical group as a whole had markedly lower levels of several inflammatory cytokines as compared with C-ME/CFS patients. Although some differences were noted in CSF cytokines based on duration of illness—a factor we previously found to profoundly affect plasma cytokine levels in ME/CFS in prior work12— adjustment for illness in our final logistic regression models did not eliminate findings of inhibited inflammatory cytokines in A-ME/CFS."
 
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Manganus

Senior Member
Messages
166
Location
Canary islands
The one difference is IL17A, which I highlighted. It has some seriously low p values and seems to consistently show difference over time between classical and atypical. I'd like to know more about what it does!
It's, as far as I know, already established to show up with high levels in several inflammatory diseases, often autoimmune, like rheumatoid arthritis and multiple sclerosis. Downstream it regulates arachidonic acid, i.e. inflammatory expression, but for the time I've forgotten whether it's up- or down regulating.
 
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Manganus

Senior Member
Messages
166
Location
Canary islands
So over time, the differences between atypical and classical are decreasing.

Trying to get a grip, I'd to give up. It's too many components, pathways and dependencies to keep track of.

However, to me it looks very much as if it is specifically the status of patients with classical onset of the illness that changes with time. The differences noted in the first p-value column are all insignificant.

The quite small group of patients (six in the "atypical, long" group) clearly calls for replication by independent institutions and other patients. Such replication must, of course, also check for the profile in other diseases and patient groups.
 

Murph

:)
Messages
1,799
However, to me it looks very much as if it is specifically the status of patients with classical onset of the illness that changes with time. .

I think one thing we can take away from this is the previous study of a change in cytokine profile between short and long duration patients is real. But only for a subgroup, being classical onset, i.e. infectious onset.
 

halcyon

Senior Member
Messages
2,482
It looks like they broke down the results based on duration of illness, which they had previously done on plasma cytokines but not CSF as far as I recall. The samples from early classic patients seem to have quite elevated interferon alpha levels. From what I can tell, this finding is highly associated specifically with (perhaps even diagnostic of) acute viral infection of the CNS, including with enteroviruses, and less so with bacterial infection and other neurological diseases. (1, 2)
 
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duncan

Senior Member
Messages
2,240
@halcyon , whatever the study demonstrates, its relevance for acute infections must by definition be limited, no? If a viral infection of the CNS is involved, including enteroviruses, those infections would not be acute. That is not to say they are not active; rather they have just moved beyond the acute phase.
 

halcyon

Senior Member
Messages
2,482
So with the inclusion criteria of studies like the NIH clinical study being meeting CDC/CCC criteria and < 5 years illness duration, presumably they will end up with all 4 of the same distinct types of ME patient from this paper (short/long classic, short/long atypical) in their cohort, with their immune parameters all over the fricking place. I really hope NIH is paying attention to this paper.
 

Murph

:)
Messages
1,799
So with the inclusion criteria of studies like the NIH clinical study being meeting CDC/CCC criteria and < 5 years illness duration, presumably they will end up with all 4 of the same distinct types of ME patient from this paper (short/long classic, short/long atypical) in their cohort, with their immune parameters all over the fricking place. I really hope NIH is paying attention to this paper.

One great thing this study could do is prompt a round of publications reviewing old data along this new dichotomy (quadchotomy?). (Come to think ... It might even be octotomy since male and female patients have also shown important differences in metabolites)

The more we know about where and how to look, the more we can see!
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Do these excerpts (my bolding) suggest that the atypical ME/CFS group were more severly affected than the 'classic' group?

The importance of lower levels of IL17A and CXCL9 in the CNS in A-ME/CFS is unclear. We speculate that subjects with unusual exposures or comorbidities may have less activation of neuroimmune signaling pathways.

IL-17A levels tended to be lower in C-ME/CFS subjects with longer duration of illness; however, levels did not differ for atypical subjects based on disease duration. This may imply an alternate, non-Th17-dependent mechanism in atypical subjects, or a more rapid progression of neurodegeneration than in classical subjects.

Careful attention to exposure histories preceding onset of illness and longitudinal surveillance for the development of unusual medical comorbidities may help to identify novel pathways underlying dysfunction in this highly debilitated patient population.

Apart from meeting case definitions I'm not sure they collected any measures of disease severity.
 

Aroa

Senior Member
Messages
109
Location
Spain
I know research is very important for our disease, but I have too many questions , as a science ignorant.

Is this sample representative of Me patients ?, Are any of these inmune abnormalities specific for Me patients ? May other people who share them not develop ME/CFS ? Will this approach help us to find a treatment in the short/medium term ?

I am desperately looking for a treatment !!!!
 
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A.B.

Senior Member
Messages
3,780
Is this sample representative of Me patients ?

As far as I understand these were patients from an outbreak that happened in the 80's.

The sample is sadly not representative. For all we know the outbreak patients could have a different illness than the rest of ME cases.

Unfortunately ME/CFS has been neglected for so long that the infrastructure and funding for bigger and more representative studies doesn't exist. The NIH is building this infrastructure right now as well as increasing funding. By infrastructure I mean centers of excellence with highly trained doctors that treat patients, collect the information and samples required for high quality studies, and recruit patients into studies.

In the meantime our researchers are doing what they can with the tools and funding they have. Once they are given better tools and more funding they will also find it easier to make progress.
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
By your rather encompassing definition, brain cancer would be included under the umbrella of neuropsychiatry, as would some channelopathies that influence cognitive function. I have seen both in action first hand, and I can vouch that both were dealt with by neurologists.

I suspect the assay panel employed in this study would be shunned in both of my examples - as I can guarantee it also would in NB.

I guess most neuropsychs would agree with your liberal definition of what the discipline should encompass. I would imagine there are many neurologists and infectious disease specialists that would limit those claims.

You have missed the point Duncan. These conditions are considered neuropsychiatry and they are dealt with by neurologists once the mental dysfunction has been correctly attributed to a structural or metabolic cause. So neuropsychiatry is the study of how such causes give rise to mental symptoms. As far as I know the is no such thing as a clinical neuropsychiatrist in the UK. There might be in the US but I doubt it. There are psychiatrists who deal with mental symptoms and neurologists to whom they pass on the neuropsychiatric problems that an MRI or blood test shows has an identifiable cause. There may be researchers who call themselves neuropsychiatrists because they deal with neuropsychiatric problems but I doubt it. I suspect they are either trained psychiatrists or trained neurologists who do neuropsychiatric research. Many happens to have trained in psychiatry but that does not matter. It is probably more pertinent to ME/CFS than training in neurology since ME/CFS has no hard neurological signs but has plenty of symptoms from abnormal higher function.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Most anti-dualists are, in my opinion, closet pro-dualist. Unless they clearly stand up as monists then dualism, acknowledged or not, needs to be considered. Indeed this is sometimes a particularly problematic form of dualism - mind and body are one, you cannot separate them, but mind is more important. They almost never discuss physical problems causing psychiatric symptoms, or the abysmal history of failure in psychogenic medicine.

Good point Alex. And of course Descartes was a strict biomedical physicalist, not a spook-body dualist. He distinguished the dynamic unit he called the soul, which he saw as a unit of action or force, from the billiard ball units we call matter. That must be right because thinking is mediated by electrical forces, not by billiard balls banging into each other. In contrast most neuroscientists today who call themselves materialists believe that thought emerge like ectoplasm from neural networks - complete nonsense incompatible with physics.
 

A.B.

Senior Member
Messages
3,780
It seems that our PACE friends are very flexible and will claim that the mind has impressive power over the body, while simultaneously claiming that CBT not leading to objectively improved health while increasing self rated health does not indicate a treatment failure.
 
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Pendergast

Spain
Messages
82
Location
Spain
Sorry for asking this but I have been reading the thread and I can´t find it (or maybe I havn´t seen it) and the full medical papers in English kill my brain.... :confused:

Could someone tell me how exactly do the researchers define Atypical and Classical types of ME? ( I´m not referring to the immune signatures they have found, but to the clinical features to make that distinction).

Thank you in advance! :hug:
 
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Could someone tell me how exactly do the researchers define Atypical and Classical types of ME? ( I don´t mean the immune signatures they have found, but to the clinical features to make that distinction).
Both atypical and classical types met either the 1994 CDC criteria and/or the 2003 Canadian consensus criteria.

Classical - ME/CFS started suddenly after a flu-like infection.

Atypical - either had prior histories of viral encephalitis, illness after foreign travel or blood transfusion, or later developed a concurrent malady—seizure disorders, multiple sclerosis-like demyelinating disorders, Gulf War Illness, or a range of cancers—at rates much higher than seen in the general population.

Think this answers your question.