Markers for CFS/ME?

[Stone]

Are there readily available tests for those abnormalities? If so, they might be great diagnostic tests.

I doubt it, but that doesn't mean that there are no biomarkers for CFS. They would be readily available if there were a market for them, naturally.

 

[Angela Kennedy]

Angela,

Well, I just sort of made that up. But its easy to just go to a mirror and check for yourself; my eyes are not Sanpaku. You may find this of interest:
http://www.bbc.co.uk/dna/h2g2/A25323518

Or this:http://www.redicecreations.com/article.php?id=4762
Three whites, or sanpaku, is common among those who are ill or exhausted. It is most severe among those who are gravely ill and approaching death.

Ok. Well- at the risk of being reported on Bad Science for having no sense of humour or a 'lack of awareness' (I have been subjected to a 'theory of mind' appraisal by them before and they do watch this forum) were you making a joke? Otherwise, why would you make it up?

I did check myself on a handmirror. I don't have CFS, alcoholism, psychoticism (as far as I know), eat too much sugar, am not Marilyn Monroe, and while I am approaching death (as are we all) it isn't apparently imminent. However, if I hold the mirror at various angles, the results are different. Do I have Sanpaku?

 

[Levi]

Well, my example was just to get the ball rolling and start some dialog. I know nothing about Sanpaku, other than that folks with it probably have small irises. Folks here are so respectful that no one called me on it til now, and I had forgotten to mention that I was making it up. At least I said "possible marker".

Net research on the topic interestingly DID lead me back to my own post in this thread, so I guess that is how bad science takes off exponentially with the internet.

(snipped) were you making a joke? Otherwise, why would you make it up?

 

[jeffrez]

It might even be true, but I doubt any mainstream doctor would take it seriously even if it were. I can easily see being laughed out of the office claiming the irises of my eyes proved I had ME/CFS.

After getting sick, I noticed a couple years later that I had developed areas of complete hair loss on the outer shin region on both of my legs. After looking into it, I found that supposedly it's a classic sign of adrenal insufficiency. A doctor even once commented on it, and when I said it's thought to be related to adrenals, she just said "uh huh," like it was just more evidence of me "somatizing," etc.

It's a no-win with these people, until there are hard and fast blood tests or other generally consistent laboratory abnormalities. Even then, they probably won't believe it (because there are now, and they still don't believe it!). Like someone said in another thread, we're probably just going to have to wait until all the older people die off, and then gradually there might be a shift. XMRV being validated might help shift things.

 

[leelaplay]

Angela,

Well, I just sort of made that up. But its easy to just go to a mirror and check for yourself; my eyes are not Sanpaku. You may find this of interest:
http://www.bbc.co.uk/dna/h2g2/A25323518

Or this:http://www.redicecreations.com/article.php?id=4762
Three whites, or sanpaku, is common among those who are ill or exhausted. It is most severe among those who are gravely ill and approaching death.

Levi - I think you're going to have to face it that this level of humour is too sophisticated for foggy-brained me, and maybe a few others. There are so many aspects of ME/CFS research that I am still not familiar with after 3/4 of a year of trying to educate myself that I thought this could be one that I hadn't heard of, like the fingerprint one, and I was too tired to check your link - was just barely able to focus on the main idea of collecting possible biomarkers and associated research.

Angela - my hat off to you for cluing in!

 

[Levi]

Shrewsbury,

Apologies! like I said, I was mainly trying to start a discussion on biomarkers, and I threw in Sanpaku as an interesting oddball item. Should have clarified. But this does get me thinking. Let's say that we actually came up with a bonifide marker or set of markers; how would you go about selecting your cohort, setting up the research, and validating the marker(s)? If XMRV pans out, this will become a very important issue.

Levi - I think you're going to have to face it that this level of humour is too sophisticated for foggy-brained me, and maybe a few others.

 

[Chris]

Klimas biomarkers

Hi, checked the DVD of Klimas' talk in London, and there she does strongly support NK cell functionality (not just numbers) as a biomarker, and goes on to suggest that "Perforin by flow cytometry is reproducible and could be a surrogate for NK cell function," which might be an easier test to do--I don't know. She also says that Neuropeptide Y bridges autonomic and immune functions and is directly impacted by soluble CD26 (another potential biomarker); NPY "correlates with severity of illness, " thus producing a potentially useful biomarker to determine whether or not a given therapy is having an effect.
With Jason doing first rate work on the huge question of definitions, Kerr doing great work on genetic indicators, Klimas getting a real handle on the biomarker issue, and Mikovits forging ahead with others on XMRV and maybe a "final solution," I think real progress is being made--hurrah for all of them and the others who are working too! Chris

 

[acer2000]

The question is if NK cell function/number decreases are specific for CFS. I suspect they are not. My CFS specialist said he sees people with acute viral infections (that they end up recovering from) who during the time they are ill also show low NK cell function and number. Their counts and function recover when their acute viral infection (ie CMV, etc..) goes away. Does anyone know if Dr. Klimas has looked at this? Do other illnesses show this abnormality?

 

[SOC]

Well, my example was just to get the ball rolling and start some dialog. I know nothing about Sanpaku, other than that folks with it probably have small irises. Folks here are so respectful that no one called me on it til now, and I had forgotten to mention that I was making it up. At least I said "possible marker".

Net research on the topic interestingly DID lead me back to my own post in this thread, so I guess that is how bad science takes off exponentially with the internet.

I think we need to consider that Levi's Sanpaku eyes criteria is as good (or maybe even better than) the revised Fukuda used in the last CDC paper.

It's nice the way nobody ripped into Levi, BTW. :Retro smile: And Angela queried him so politely! We may be memory-impaired, maybe even humor-impaired sometimes, but I'm glad to see we're not good manners-impaired.

 

[SOC]

The question is if NK cell function/number decreases are specific for CFS. I suspect they are not. My CFS specialist said he sees people with acute viral infections (that they end up recovering from) who during the time they are ill also show low NK cell function and number. Their counts and function recover when their acute viral infection (ie CMV, etc..) goes away. Does anyone know if Dr. Klimas has looked at this? Do other illnesses show this abnormality?

I'm confident low NK cell count is not specific enough to ME/CFS to be a marker, but I thought low NK cell function was. I wonder if the NK function values your CFS specialist sees with acute CMV infection are as low as the numbers Klimas is seeing. Did Klimas see normal NK cell count and low NK cell function, or both low in ME/CFS patients. I guess this needs more work.

What if we combined NK cell function with another test, like the Pacific Labs PEM test. Do we know if a segment of ME/CFS patients does not show PEM on that test?

 

[Tammie]

I am not looking at either rt now, so I could be wrong, but I think that both Dr Hooper's paper, "Magical Medicine; How to Make a Disease Disappear" and the Canadian Criteria paper have some specific bio markers in them, too

 

[shiso]

I'm confident low NK cell count is not specific enough to ME/CFS to be a marker, but I thought low NK cell function was. I wonder if the NK function values your CFS specialist sees with acute CMV infection are as low as the numbers Klimas is seeing. Did Klimas see normal NK cell count and low NK cell function, or both low in ME/CFS patients. I guess this needs more work.

What if we combined NK cell function with another test, like the Pacific Labs PEM test. Do we know if a segment of ME/CFS patients does not show PEM on that test?

I think abnormally low NK cell function is pretty widely accepted as showing up in almost all patients, as Dr. Peterson has mentioned in interviews (sorry no source, just from memory). I like the idea of "NK cell function plus a, b, and/or c."

I don't think the Pacific Fatigue Lab repeat test is anywhere near definitive though, unfortunately, even though it nicely documents lower energy production via lower V02 max after the second test in many patients. Not everyone with ME/CFS shows lower numbers via the test, even though they experience PEM. There was a thread on the topic here maybe a year ago (I can't find it now). I think the numbers from even their original published study were significant but nowhere near 100%.

I like the other markers people have mentioned. Not everyone will be positive for all tests, but like SSDI uses a number of test findings to determine disability, there definitely seems to be a footprint (is that the right word?) where taken together, clear patterns of abnormal test results for a range of tests empirically found to be abnormal in ME/CFS patients are likely to emerge - that are likely to be useful for research purposes. The problem is that these disparate tests (immune function testing catered to abnormalities found in ME/CFS research, tilt table, cardiopulmonary testing, SPECT, XMRV, etc.) are not readily accessible to the vast majority of patients due to the dearth of clinicians and researchers who know what to look for and how to look for them.

 

[SOC]

I think abnormally low NK cell function is pretty widely accepted as showing up in almost all patients, as Dr. Peterson has mentioned in interviews (sorry no source, just from memory). I like the idea of "NK cell function plus a, b, and/or c."

I don't think the Pacific Fatigue Lab repeat test is anywhere near definitive though, unfortunately, even though it nicely documents lower energy production via lower V02 max after the second test in many patients. Not everyone with ME/CFS shows lower numbers via the test, even though they experience PEM. There was a thread on the topic here maybe a year ago (I can't find it now). I think the numbers from even their original published study were significant but nowhere near 100%.

This isn't going to be easy or one of our brilliant ME/CFS specialists would have come up with a simple diagnostic protocol. :Retro smile:

Next question, already raised by someone -- who other than ME/CFS patients has NK function in the range Dr Klimas has reported for ME/CFS patients? Can we say something like,
Test NK cell function, if in range (whatever) and patient tests negative for X,Y,Z, then diagnosis is ME/CFS....?

If PEM is distinctive in ME/CFS, but the Pacific Labs test doesn't always catch it, could their test (or something like it) be used as a second-level test? For example,
If NK cell function is normal but patient exhibits symptoms of ME/CFS, test for PEM using (whatever)...?

By this path the patient would have to be "normal" by both NK cell function and PEM test to be declared negative for ME/CFS. Looked at the other way, the patients would be positive for ME/CFS if s/he was positive on the NK cell function test or the PEM test.

Can anybody take a guess at what percentage of ME/CFS patients would be missed by both tests and conversely how many non-ME/CFS patients would be included by this protocol?

 

[ahimsa]

I skimmed this thread but didn't see a link for this paper which talks about biomarkers for CFS (Klimas is one of the authors as you can see).

PLoS One. 2010 May 25;5(5):e10817.

Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26.

Fletcher MA, Zeng XR, Maher K, Levis S, Hurwitz B, Antoni M, Broderick G, Klimas NG.

Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. mfletche@med.miami.edu

Abstract

BACKGROUND: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC) and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV) also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.

METHODS/RESULTS: Subjects included female and male CFS cases and healthy controls. NK cell function was measured with a bioassay, using K562 cells and (51)Cr release. Lymphocyte associated DPPIV/CD26 was assayed by qualitative and quantitative flow cytometry. Serum DPPIV/CD26 was measured by ELISA. Analysis by receiver operating characteristic (ROC) curve assessed biomarker potential. Cytotoxic function of NK cells for 176 CFS subjects was significantly lower than in the 230 controls. According to ROC analysis, NKCC was a good predictor of CFS status. There was no significant difference in NK cell counts between cases and controls. Percent CD2+ lymphocytes (T cells and NK cells) positive for DPPIV/C26 was elevated in CFS cases, but there was a decrease in the number of molecules (rMol) of DPPIV/C26 expressed on T cells and NK cells and a decrease in the soluble form of the enzyme in serum. Analyses by ROC curves indicated that all three measurements of DPPIV/CD26 demonstrated potential as biomarkers for CFS. None of the DPPIV/C26 assays were significantly correlated with NKCC.

CONCLUSIONS: By ROC analysis, NKCC and three methods of measuring DPPIV/C26 examined in this study had potential as biomarkers for CFS. Of these, NKCC, %CD2+CD26+ lymphocytes and rMol CD26/CD2+ lymphocyte, required flow cytometry, fresh blood and access to a high complexity laboratory. Soluble DPPIV/C26 in serum is done with a standard ELISA assay, or with other soluble factors in a multiplex type of ELISA. Dipeptidyl peptidase IV on lymphocytes or in serum was not predictive of NKCC suggesting that these should be considered as non-redundant biomarkers. Abnormalities in DPPIV/CD26 and in NK cell function have particular relevance to the possible role of infection in the initiation and/or the persistence of CFS.

It was over my head but I think it confirms what others have posted - it's not the NK cell count itself that is different but decreased natural killer cell cytotoxicity (NKCC) and some other items (none of which I really understood).

Anyway, here are links to the abstract and full paper:

http://www.ncbi.nlm.nih.gov/pubmed/20520837
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876037/?tool=pubmed