Can ME/CFS patients in the UK choose who they go to see on the NHS?

[alex3619]

I think we need to separate the notion of diagnostic biomarkers and outcome biomarkers. The 2 day CPET is currently an outcome biomarker. So are other things in all probability, but they need more work.

Our first widespread diagnostic test might not go to the core of the disease process/es. In time these will be identified though, and we will get better biomarkers.

The issue with the 2 day CPET to me is that its been around since the first half of last century, and its an obvious test. From a clinical perspective it tells you, objectively, what treatment is doing. This is critical from a clinical outcomes viewpoint.

I don't think its an ideal test, I suspect it may be rapidly superseded, but its what we have now.

 

[Marco]

@Jonathan Edwards

In the context of what if anything can be done for ME/CFS patients, one of the most consistent findings (with several recent papers) is autonomic dysfunction manifesting as symptoms such as POTS etc. As I understand it autonomic dysfunction is associated with increased morbidity and mortality and may be a treatable condition with the best outcomes when tacked early. .

Although discussed in the context of diabetic autonomic neuropathy (which may lead to cardiac autonomic neuropathy) Vinik and Murray, 2008 (link below) includes the following quote :

“medical leadership including the American Diabetes Association (ADA), the American Heart Association, the American Academy of Neurology, the American Academy of Family Physicians, the Juvenile Diabetes Research Foundation International, and the National Institutes of Health have published recommendations for autonomic testing as part of the standard of care for chronic diseases.”

http://www.touchendocrinology.com/articles/autonomic-neuropathy-treatable

As ME/CFS is a chronic 'disease' where autonomic dysfunction appears to be common and where treatments are available and 'non-controversial', would you agree that at least testing for autonomic dysfunction should be a standard approach to care and management of the condition, even if autonomic dysfunction is just a downstream symptom?

 

[justy]

People talk about low NK cell function a lot, but there are some of us here, myself included who have classic M.E symptoms, but actually have high NK cell activity - it is easy to presume all PWME have low function. I have no idea what this means, just pointing it out.

 

[Marco]

People talk about low NK cell function a lot, but there are some of us here, myself included who have classic M.E symptoms, but actually have high NK cell activity - it is easy to presume all PWME have low function. I have no idea what this means, just pointing it out.

Despite the focus on this I'm not sure it means a lot. Oxidative stress can cause it. The only interesting aspect to this I've found is that CD56 bright NK cell counts may be used to determine how effective the monoclonal antibody daclizumab is in the treatment of relapsing/remitting multiple sclerosis (RRMS).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458677/

 

[Jonathan Edwards]

Or might the psychiatric argument be that prior inactivity caused the low NK function, and if so, how long ago and for how long could inactivity lower NK function (sorry about the muddled syntax - it's morning!)?

Yes, as long as there is some way to make the link there may be some who will dismiss something like low NK activity. But you are right that if there was some sort of dose response curve, or in this case an absence of a dose response relation to activity then the argument would be much stronger. But before that we need to find out why the NK findings are not confirmed by some labs. We need an observation that you can repeat anywhere. My suspicion is that the reasons for the variation may not be that hard to identify. It just requires a concerted effort to track them down.

 

[Jonathan Edwards]

People talk about low NK cell function a lot, but there are some of us here, myself included who have classic M.E symptoms, but actually have high NK cell activity - it is easy to presume all PWME have low function. I have no idea what this means, just pointing it out.

Yes, I don't think even the people working on low NK function would want us to think they thought all types of ME would have low NK activity. There would be no problem in there being some sorts of ME with high levels. In my speculation of 6 types we could easily have one high and one low. But it is likely that the types come in much the same proportions across the world and if it true that the average mix has low average NK function and we can repeat that time and again we have what we need. We can also probably say that thos ewith high NK activity may belong to a minor subgroup.

As Marco says, all sorts of things can depress NK function, but that does not necessarily negate its value as a starter marker' from which the causes can be unravelled. I am not sure where I would lay my bets but I think it deserves more work.

 

[Sasha]

Yes, as long as there is some way to make the link there may be some who will dismiss something like low NK activity. But you are right that if there was some sort of dose response curve, or in this case an absence of a dose response relation to activity then the argument would be much stronger. But before that we need to find out why the NK findings are not confirmed by some labs. We need an observation that you can repeat anywhere. My suspicion is that the reasons for the variation may not be that hard to identify. It just requires a concerted effort to track them down.

I seem to remember Nancy Klimas saying that the NK findings are consistent if you look at recent studies using modern tests, and with large enough numbers to cut down on statistical noise - I wouldn't trust my memory on this, though. Ring a bell with anyone?

 

[MeSci]

Yes, as long as there is some way to make the link there may be some who will dismiss something like low NK activity. But you are right that if there was some sort of dose response curve, or in this case an absence of a dose response relation to activity then the argument would be much stronger. But before that we need to find out why the NK findings are not confirmed by some labs. We need an observation that you can repeat anywhere. My suspicion is that the reasons for the variation may not be that hard to identify. It just requires a concerted effort to track them down.

Erica Verrillo noted the inconsistency of immune findings in a blogpost republished here, including reference to reasons for variation, e.g.

Some studies indicated that there were increased pro-inflammatory cytokines, others found increased anti-inflammatory cytokines.

Given the fact that one of the hallmarks of CFIDS is waxing and waning symptoms, this "inconsistency" should not have come as a surprise. The immune dysfunction that characterizes CFIDS is that it both under- and over-responds. Immune, as well as neuro-endocrine, swings are the inevitable outcome of the loss of homeostasis that lies at the heart of the illness.

and

In 2012, a group of Australian researchers headed by Ekua Brenu completed the first longitudinal study of immune function in patients with CFS/ME (CFIDS). This was the first time researchers had examined immune function over a long period of time, in this case, 12 months. The value of longitudinal studies to measure immune function is that the immune system is a moving target. It responds instantly to environmental input. Even the best short-term study of the immune system can’t give researchers more than a snapshot.

She does say that NK function is consistently low, but I guess that is because not enough research has been done or published, or maybe people like @justy have been misdiagnosed, as seems to be very common.

 

[Jonathan Edwards]

She does say that NK function is consistently low, but I guess that is because not enough research has been done or published, or maybe people like @justy have been misdiagnosed, as seems to be very common.

As indicated in the earlier post I think it may still be perfectly true that ME in toto shows low NK activity but that within this there are subgroups where it is high. I doubt Dr Klimas would have difficulty with that. If Justy has ME16 but most people have ME1-9, that does not mean Justy is misdiagnosed to my mind!

 

[NK17]

Just my personal anecdotal input regarding low NK function, which does not mean that I consider this a universal ME blood biomarker.

The very first time I got tested (by Dr. Kogelnik), was back in 2011 right after a long vacation in Italy (my last one), back then I was not bedbound nor homebound, I was still up right, walking and the result was 17 LU.

Next test was in March 2012, after several months on high dose Famvir (for herpes viruses chronic infections) when I was still driving, cooking, groceries shopping and relatively active (doing yoga once a week). I was tested at the same time as a close young blood relative and we both had low NK functions, precisely 9 and 8!

In the spring of 2012 I started to have to slow down most activities and my NK function was 11 LU.

In 2013 I started to suffer from clear autonomic dysfunction. I slowly had to give up driving, all physical activities, most prep for cooking for meals had to be carefully done while sitting, had reduced groceries shopping to once a week and my NK function was 5 LU.

To me this smells like my NK function is clearly linked to the progression of my type of ME. I also have a family history of lymphoma, glandular fever and CVID.

It's all tied up together and Dr. Nancy Klimas has been reporting abnormalities in the NK cells in her large ME patients' group.

The disease has been talking to us for a while, it's just a matter of one more sustained international push and we'll get one biomarker or a cluster of biomarkers, which might correlate to the disease progression and/or the spectrum quality of the MEs subgroups.

I think the Japanese have been calling ME/CFS a low NK cells disorder, since the 80's or 90's!

Dr. Sonya Marshall-Gradisnik @ Griffith University in Australia is working on this specific immunological aspects and will soon be testing the most severe cases of ME patients.

NK cells have been recently implicated in MS and some PWME have white matter lesions, which are non specific, just because most doctors are too ignorant and not curious enough to read the CCC and ICC to actually link them with ME.

NK will become one of the tests that will tie together the immunological dysfunction that is present in PWME, at some point or another, and will help in the diagnosis and treatment of the disease.

 

[MeSci]

As indicated in the earlier post I think it may still be perfectly true that ME in toto shows low NK activity but that within this there are subgroups where it is high. I doubt Dr Klimas would have difficulty with that. If Justy has ME16 but most people have ME1-9, that does not mean Justy is misdiagnosed to my mind!

True - it may come down to how we define ME!

 

[A.B.]

NK cell count and function are NOT the same, right? One is the number of cells per unit of blood, the other is measured how?

 

[MeSci]

NK cell count and function are NOT the same, right? One is the number of cells per unit of blood, the other is measured how?

Thanks for the reminder. I knew this but had forgotten! No idea how function is measured.

@Jonathan Edwards...?

 

[NK17]

NK cell count and function are NOT the same, right? One is the number of cells per unit of blood, the other is measured how?

Right.
But maybe somebody else can articulate on this, since I'm about to crash and the day after tomorrow I'll take the 2 day CPET ;(.
FYI I've just got NK function tested before the CPET and will retest after; results are pending .

 

[Leopardtail]

You will understand that I am not suggesting that there is ONE reproducible biomarker to be found. There should be lots, some specific for individual subgroups and some more general perhaps.

Another key factor is the need to get around the problem of biasing in population studies. If we are looking for something that turns up as a statistically increased frequency, which is likely, then it is no good studying populations of PWME that for some reason or other are unrepresentative of the problem as a whole. There is probably a need for a study like the Norfolk Arthritis Register which studied a whole population, unselected. That way there was no bias from the way doctors had already pre-labelled patients before the analysis.

The most troubling thing about 'bias' is that due to the large number of specialities involved in ME patients (with their GPs) may well be self-selecting by virtue of their particular symptom profiles.

E.g. @MeSci takes an immune view of the disease due to her reading of the science and her particular symptoms. By contrast I have relatively few immune issues beyond a degree of under-function but marked problems with Mitochondria and Endocrine function. We are polar opposites in some of our symptoms. As such we would each push for a different kind of referral, be interested in participating in different studies, and be identified as needing different help by out GPs (if all worked well). This is of course on top of researchers choosing their own selection criteria to suit their interest!

This comes back to the project I have begun discussing with you that attempts to do the fundamental first science: identify the groups, and standardise the reporting. If research is done on the whole population, we need to be able to identify on whom it worked, on whom it didn't.

 

[heapsreal]

People talk about low NK cell function a lot, but there are some of us here, myself included who have classic M.E symptoms, but actually have high NK cell activity - it is easy to presume all PWME have low function. I have no idea what this means, just pointing it out.

I think it could be a reason that the australian researchers seperated the nk function into bright and dim cells. I did several over an 18month period in this study, i probably wasnt really supppose to do this but i took an immune mod cycloferon before one test and it shot my nk function way above normal range but my nk bright cells were still low. this type of testing i believe is still a research test, so its hard to get outside of the research setting.

I think the reason they also did other testing was because of people like yourself, maybe u have a low cd8 t cell function?? I think they need to have a pool of core tests and test positive for a majority as well as tick the boxes for the CCC. I think the nk function test alone isnt the answer, but i think adding some of these tests to the CCC would help refine the group and have a more accurate diagnosed group of people that they could use for research too instead of having a mixed bag of people with depression and other disorders that dont have ME??

 

[heapsreal]

Just my personal anecdotal input regarding low NK function, which does not mean that I consider this a universal ME blood biomarker.

The very first time I got tested (by Dr. Kogelnik), was back in 2011 right after a long vacation in Italy (my last one), back then I was not bedbound nor homebound, I was still up right, walking and the result was 17 LU.

Next test was in March 2012, after several months on high dose Famvir (for herpes viruses chronic infections) when I was still driving, cooking, groceries shopping and relatively active (doing yoga once a week). I was tested at the same time as a close young blood relative and we both had low NK functions, precisely 9 and 8!

In the spring of 2012 I started to have to slow down most activities and my NK function was 11 LU.

In 2013 I started to suffer from clear autonomic dysfunction. I slowly had to give up driving, all physical activities, most prep for cooking for meals had to be carefully done while sitting, had reduced groceries shopping to once a week and my NK function was 5 LU.

To me this smells like my NK function is clearly linked to the progression of my type of ME. I also have a family history of lymphoma, glandular fever and CVID.

It's all tied up together and Dr. Nancy Klimas has been reporting abnormalities in the NK cells in her large ME patients' group.

The disease has been talking to us for a while, it's just a matter of one more sustained international push and we'll get one biomarker or a cluster of biomarkers, which might correlate to the disease progression and/or the spectrum quality of the MEs subgroups.

I think the Japanese have been calling ME/CFS a low NK cells disorder, since the 80's or 90's!

Dr. Sonya Marshall-Gradisnik @ Griffith University in Australia is working on this specific immunological aspects and will soon be testing the most severe cases of ME patients.

NK cells have been recently implicated in MS and some PWME have white matter lesions, which are non specific, just because most doctors are too ignorant and not curious enough to read the CCC and ICC to actually link them with ME.

NK will become one of the tests that will tie together the immunological dysfunction that is present in PWME, at some point or another, and will help in the diagnosis and treatment of the disease.

I believe the australian researchers are also looking into comparing nk function, bright and dim cell function with MS and RA disorders. Im sure while they have the blood they will be measuring other immune signals like cytokines etc

 

[heapsreal]

Right.
But maybe somebody else can articulate on this, since I'm about to crash and the day after tomorrow I'll take the 2 day CPET ;(.
FYI I've just got NK function tested before the CPET and will retest after; results are pending .

That will be interesting NK

 

[Leopardtail]

People talk about low NK cell function a lot, but there are some of us here, myself included who have classic M.E symptoms, but actually have high NK cell activity - it is easy to presume all PWME have low function. I have no idea what this means, just pointing it out.

This seems to be true of most aspects of ME doesn't it? We near all seems to have poor Mito function. But with adrenaline, Cortisol, T4, B12 some of us are low, some high, the only uncommon things seems to be 'having something within 1STD or mean'.

We really need to have a much better idea of how these differences correlate.

 

[Leopardtail]

Right.
But maybe somebody else can articulate on this, since I'm about to crash and the day after tomorrow I'll take the 2 day CPET ;(.
FYI I've just got NK function tested before the CPET and will retest after; results are pending .

It will be very interesting to see whether your results are stable (ie inherent) or variable (a function of fatigue level).
@Jonathan Edwards how rapidly does the profusion and activity level of a NK cell change?
What is their half-life (or life span) in the blood stream?