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

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
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.

Cort Johnson posted a comment on one of his blogs recently. What is currently being seen, though I think unpublished, is the same NK cells both have a high and a low function, depending on the testing. Isolated NK cells test fine. NK cells in blood or serum test nonfunctional. Something is turning them off that is in the blood or serum.

However I currently cannot reconcile this with the finding of altered cell surface markers on our NK cells, in particularly the lack of bright cells. Yet marker expression may be subject to rapid change, so I simply don't know.

The lesson here is that ME involves regulatory issues. The circumstances surrounding most testing are critical. Test two different ways and you might get different results. We already see this with immune markers post exercise, and energy production post exercise. It takes an appropriate challenge to induce the problem to be measured. At rest and in some controlled conditions things appear normal.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
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?

There is probably a book, or at least a chapter, to write about the complexity of NK measurements. Number and function are certainly different but presumably if numbers are low that will contribute to low functionality if all else is equal. Trouble is that all else is not likely to be equal.

Function is usually measured by the ability to kill (as in natural killer) certain standard types of cell. Cells from the immortal K562 cell line are often used as victims. What has complicated things recently is the knowledge that whether or not NK cells will kill probably depends on recognising HLA antigens on the victims. Weirdly this is not a 'self-nonself' distinction. Certain people's NK cells will recognise certain HLA types but that has nothing to do with whether those people actually possess that type themselves. Anyway, it seems likely that unless you take this into account you may not be able to draw useful conclusions from using K562 cells. And for the rest of the book... someone on the list probably knows more than I do but I think the bottom line is that nobody really knows what these function tests mean for real people. As far as I know there is no serious disease due to complete absence of NK cells known.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Cort Johnson posted a comment on one of his blogs recently. What is currently being seen, though I think unpublished, is the same NK cells both have a high and a low function, depending on the testing. Isolated NK cells test fine. NK cells in blood or serum test nonfunctional. Something is turning them off that is in the blood or serum.

However I currently cannot reconcile this with the finding of altered cell surface markers on our NK cells, in particularly the lack of bright cells. Yet marker expression may be subject to rapid change, so I simply don't know.

Sorry if this is a silly question, but I haven't been awake for long! If the NK cells have the same cell surface markers in blood and in isolation, doesn't this suggest that something in the blood is attracted to the markers and consequently reduces the cell function?
 

Leopardtail

Senior Member
Messages
1,151
Location
England
There is probably a book, or at least a chapter, to write about the complexity of NK measurements. Number and function are certainly different but presumably if numbers are low that will contribute to low functionality if all else is equal. Trouble is that all else is not likely to be equal.

Function is usually measured by the ability to kill (as in natural killer) certain standard types of cell. Cells from the immortal K562 cell line are often used as victims. What has complicated things recently is the knowledge that whether or not NK cells will kill probably depends on recognising HLA antigens on the victims. Weirdly this is not a 'self-nonself' distinction. Certain people's NK cells will recognise certain HLA types but that has nothing to do with whether those people actually possess that type themselves. Anyway, it seems likely that unless you take this into account you may not be able to draw useful conclusions from using K562 cells. And for the rest of the book... someone on the list probably knows more than I do but I think the bottom line is that nobody really knows what these function tests mean for real people. As far as I know there is no serious disease due to complete absence of NK cells known.
I saw something a short while ago that discussed NK cells dealing with 'failing cells' cancerous of otherwise, making them a general 'caretaker' of stuff that should not (or no longer) be there. Does this have anything to do with that 'weird self-nonself' thing you mentioned?
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Sorry if this is a silly question, but I haven't been awake for long! If the NK cells have the same cell surface markers in blood and in isolation, doesn't this suggest that something in the blood is attracted to the markers and consequently reduces the cell function?
Do you mean that occurs just in ME patients, or generally?
 

Leopardtail

Senior Member
Messages
1,151
Location
England
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.
Perhaps this comes back to the point that started the thread.. We are not a single group. I know that our local ME support group has two people with superb immunity who never get a cold... but substantially more people who tend to go through hell with infections in winter.
Pretty much every symptoms seems to have people at both ends of the spectrum.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
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!

I think that you are somewhat misconstruing and misrepresenting my position. Like most sufferers, I have multisystem symptomatology. I also read scientific papers and discussions on multiple potential causes, subgroups, etc.

What I am most interested in (as I think are we all) is how to address the fundamental cause(s) of the illness. This may differ in different people. I have addressed this in my main 'leaky gut' blogpost.

I currently find the leaky-gut/autoimmunity theory most compelling, at least for my own pattern of illness development and symptomatology, and it seems to fit well for many others too. Many of us have found that addressing the basis of this has brought about considerable improvement, although recovery is of course elusive. Others have not seen such improvements, and sometimes improvements cease after a promising start.

I remain open to all credible scientific evidence on this and other theories.
 

A.B.

Senior Member
Messages
3,780
Whatever illness I have, there is nothing to suggest an infectious component. I actually get infections much less often than before (but the common sense explanation might just be that I have less contact with other people and am therefore less exposed).

And for what it's worth, my NK cell count was 31% on a scale of 2-30%. Cytotoxic T cells were a bit low, 12% on a scale of 16-37%, but according to the lab this is within the norm.

On the other hand, there are very sudden fluctuations in symptoms, sudden deterioration within hours, lasting weeks or even months, for no apparent reason. I think this is consistent with some autoimmune problem. This is not PEM. It happens even when I'm well rested.
 
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Sasha

Fine, thank you
Messages
17,863
Location
UK
Perhaps this comes back to the point that started the thread.. We are not a single group. I know that our local ME support group has two people with superb immunity who never get a cold... but substantially more people who tend to go through hell with infections in winter.
Pretty much every symptoms seems to have people at both ends of the spectrum.

During my first bout of ME (seven years bedbound) I didn't catch a single cold. In the run-up to that period, when I already had ME but was still partly functional, I caught a cold and when symptoms suddenly started (streaming nose, etc.), I felt epic! Absolutely fantastic! After a 90% remission of some years, and now having been housebound/bedbound for some more years, I now catch everything and dread the winter. I seem to be both of these types in one (at different stages of my illness).
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Whatever illness I have, there is nothing to suggest an infectious component. I actually get infections much less often than before (but the common sense explanation might just be that I have less contact with other people and am therefore less exposed).

And for what it's worth, my NK cell count was 31% on a scale of 2-30%. Cytotoxic T cells were a bit low, 12% on a scale of 16-37%, but according to the lab this is within the norm.

On the other hand, there are very sudden fluctuations in symptoms, sudden deterioration within hours, lasting weeks or even months, for no apparent reason. I think this is consistent with some autoimmune problem.
For me this varied with severity, with mild ME I was infection proof, seldom got anything and shook them off in a day. Now though it's become a real issue. I know there is marked variation among the ME sufferers I know.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
During my first bout of ME (seven years bedbound) I didn't catch a single cold. In the run-up to that period, when I already had ME but was still partly functional, I caught a cold and when symptoms suddenly started (streaming nose, etc.), I felt epic! Absolutely fantastic! After a 90% remission of some years, and now having been housebound/bedbound for some more years, I now catch everything and dread the winter. I seem to be both of these types in one (at different stages of my illness).
Perhaps you ought to go to your local GP surgery and snog everybody with a cold once weekly :devil:
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
Others on this thread have made the point that there are investigations that would make sense to do for us (tilt-table testing as standard, for example) to reveal conditions that could at least partly be treated, but my focus here has been on trying to address the core pathology in some way.

I agree that investigation by GPs is often inadequate (I have had that problem too). But again we need to be sure the request for testing is justified. As you say, the test that most people use as an example is something like TTT for orthostatic intolerance. I would like to know more about this.

As I understand it many PWME get orthostatic intolerance. That is easy enough to establish from symptoms. So the question is what does a test add. It might provide a measure to use in research studies or drug trials but does it help in routine care? What worries me is that a tilt test may confirm 'greying out' really is orthostatic intolerance but it does not tell us the cause. 'POTS' is a technical term for a physiological effect and it may have many causes. Some might be primary defects in the autonomic nervous system, like an autonomic neuropathy, some might be protective feedback responses to e.g. cytokines, some might relate to deconditioning. Any treatments used might relieve the symptoms in one case and not another. Moreover, symptom relief might go with a long term benefit in some but a long term adverse effect in others. If the orthostatic intolerance is a protective feedback response treatments might aggravate things long term. The point is that I don't think one can assume that treatments that are useful in one context are appropriate in the context of ME unless someone has done some careful long term monitoring.

I would still be interested to know what treatments have actually been through formal trials for orthostatic intolerance, whether or not in the ME context. Some of the things I see recommended I would certainly be very wary of - like mineralocorticoid steroids. They may be a godsend to some people but I would not want GPs who do not really understand even the little we understand about ME handing out steroids. The handing out of steroids in rheumatoid arthritis caused a major medical catastrophe for thousands of people.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
So distilling the immune system variations out we have:
  • apparent lack of infection either due to poor immune response preventing symptoms or excellent function preventing infection
  • poor function causing long lasting infection
  • infection causing symptomatic improvement
  • infection causing marked increase in fatigue
Any more items folks?

@MeSci - what would you add on the 'allergic' end of the spectrum?
@Hip, @alex3619 , @Freddd do any of your have further ideas?
 
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Leopardtail

Senior Member
Messages
1,151
Location
England
I agree that investigation by GPs is often inadequate (I have had that problem too). But again we need to be sure the request for testing is justified. As you say, the test that most people use as an example is something like TTT for orthostatic intolerance. I would like to know more about this.

As I understand it many PWME get orthostatic intolerance. That is easy enough to establish from symptoms. So the question is what does a test add. It might provide a measure to use in research studies or drug trials but does it help in routine care? What worries me is that a tilt test may confirm 'greying out' really is orthostatic intolerance but it does not tell us the cause. 'POTS' is a technical term for a physiological effect and it may have many causes. Some might be primary defects in the autonomic nervous system, like an autonomic neuropathy, some might be protective feedback responses to e.g. cytokines, some might relate to deconditioning. Any treatments used might relieve the symptoms in one case and not another. Moreover, symptom relief might go with a long term benefit in some but a long term adverse effect in others. If the orthostatic intolerance is a protective feedback response treatments might aggravate things long term. The point is that I don't think one can assume that treatments that are useful in one context are appropriate in the context of ME unless someone has done some careful long term monitoring.

I would still be interested to know what treatments have actually been through formal trials for orthostatic intolerance, whether or not in the ME context. Some of the things I see recommended I would certainly be very wary of - like mineralocorticoid steroids. They may be a godsend to some people but I would not want GPs who do not really understand even the little we understand about ME handing out steroids. The handing out of steroids in rheumatoid arthritis caused a major medical catastrophe for thousands of people.
The steroids are a particular concern for me in ME. There are tendencies by some doctors to give doses too large for ME patients, and in others to not even consider. If one engages with enough people with ME a pattern falls out: @5mg of less (Cortisol) there seems to be a pattern (needing more formal research) of more benefit and lower risk. The second the dose goes to 10mg or above, the results seem mostly negative.
Do you think there may be a case for doing research into the common treatments for our component ailments and assessing whether we need the same dosage?

Also whether the common practice by some specialists (across the board) of starting below the usual minimum dose and titrating slowly upwards does indeed widely produce better results?

Clinical experience does matter, an my experience backs up that approach. However I would like to see it scientifically verified (or dis-proven).
 

Leopardtail

Senior Member
Messages
1,151
Location
England
I agree that investigation by GPs is often inadequate (I have had that problem too). But again we need to be sure the request for testing is justified. As you say, the test that most people use as an example is something like TTT for orthostatic intolerance. I would like to know more about this.

As I understand it many PWME get orthostatic intolerance. That is easy enough to establish from symptoms. So the question is what does a test add. It might provide a measure to use in research studies or drug trials but does it help in routine care? What worries me is that a tilt test may confirm 'greying out' really is orthostatic intolerance but it does not tell us the cause. 'POTS' is a technical term for a physiological effect and it may have many causes. Some might be primary defects in the autonomic nervous system, like an autonomic neuropathy, some might be protective feedback responses to e.g. cytokines, some might relate to deconditioning. Any treatments used might relieve the symptoms in one case and not another. Moreover, symptom relief might go with a long term benefit in some but a long term adverse effect in others. If the orthostatic intolerance is a protective feedback response treatments might aggravate things long term. The point is that I don't think one can assume that treatments that are useful in one context are appropriate in the context of ME unless someone has done some careful long term monitoring.

I would still be interested to know what treatments have actually been through formal trials for orthostatic intolerance, whether or not in the ME context. Some of the things I see recommended I would certainly be very wary of - like mineralocorticoid steroids. They may be a godsend to some people but I would not want GPs who do not really understand even the little we understand about ME handing out steroids. The handing out of steroids in rheumatoid arthritis caused a major medical catastrophe for thousands of people.
I like this post a lot.

Julia Newton did something on this quite recently. She assessed a large number of ME patients both for OI and causes of it. As might be expected she found various causes of it. As you rightly point out the various common causes need to be known along with their distribution in ME patients and we then need to know whether the same treatments work and whether they should be applied at the same doses. As yet publication has not occurred, one can only view her presentation video.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
But it is genuinely very difficult to know where to start researching. We still do not have reliable biomarkers to use as a handhold.

I think you mentioned earlier that response to Rituximab could be considered a biomarker. I'm still surprised (my surprise on this whole situation just never abates!) that the consultants I've seen (an immunologist and an infectious disease specialist), both convinced that I have an immune system problem that's causing my ME, won't try an immune therapy on me to see if it works, but maybe that's my naivety about the risk/benefit ratio. However, their refusal to treat hasn't been presented to me in those terms: I wonder if they are overfocused on the risk and ignoring the fact that I've been very ill for years and am actively suffering in the absence of treatment. Many of us, me included, look and act well when we visit consultants: we've rested up before and we crash later. I wonder if they really grasp the consequences of continued inaction.

Ah well! Perhaps we'll just have to differ on this one.

There are such people with no diagnosis and clinicians tend to want to try something if they can but for the symptoms of ME it is genuinely very difficult to know what to try. One can be pretty sure 99% of things one could try would do no good or have adverse effects. That is not a good place to start for just picking something at random. But I do think you are right that it has become acceptable to take inaction in ME as having some strange justification - essentially because nobody really believes there is any altered physiology.

I've been fortunate and the consultants I've encountered have all been positive that I've got an immune problem. I don't think that's the issue (although it will certainly be the issue in those who believe ME is psychosomatic). I think there's something else going on that leads of the undiagnosed receiving speculative treatment and PWME getting nothing.

So I keep coming back to agreeing that you are getting a raw deal, but not feeling that I should be persuading colleagues to try anything specific at present.

Fair enough. I think we're a bit further on from needing to try things at random and that there are therapies that are relatively low-risk that could be tried (low-dose naltrexone, for example) before the bigger-risk stuff but again, I think we'll have to agree to differ.

I think its hard to say. But what I do think is that if we can just get some consensus on one reproducible biomarker and get that published in a major journal the whole attitude to ME should change. And remember that almost all drugs in rheumatology are 'borrowed' from developments in other specialities. All we need is for the transplant people to come up with some new immune modulator and we suddenly find we have something that can be used on a compassionate basis for ME as well.

Roll on that happy day!

In the meantime, I think you make very good points about the quality of reporting (not to mention the need for reporting at all) from specialist ME/CFS clinicians overseas who have the freedom to prescribe things that UK clinicians don't. There seems to be a lot of wasted opportunity there.
 
Messages
15,786
As I understand it many PWME get orthostatic intolerance. That is easy enough to establish from symptoms.
From what I recall in the research, it's something like 95% of ME/CFS patients have NMH and/or POTS. So not just "many" but rather nearly all of us.
What worries me is that a tilt test may confirm 'greying out' really is orthostatic intolerance but it does not tell us the cause.
It can show specific blood pressure reactions to orthostatic challenge, which can give relevant specialists a good idea of what to try for treatment. Additional testing can also then be ordered to find a more proximate cause of the OI, such as norepinephrine levels, blood volume, certain auto-antibodies, diabetes insipidus, etc etc.
'POTS' is a technical term for a physiological effect and it may have many causes.
Most ME/CFS patients actually have NMH, not POTS. But POTS is better understood and easier to say, hence a lot of people with NMH talk about their "POTS" when it's not what they actually have. But that's a somewhat irrelevant matter of terminology, despite doctors often liking to shut down if a patient uses a technically incorrect term at any point :rolleyes:
Any treatments used might relieve the symptoms in one case and not another. Moreover, symptom relief might go with a long term benefit in some but a long term adverse effect in others. If the orthostatic intolerance is a protective feedback response treatments might aggravate things long term. The point is that I don't think one can assume that treatments that are useful in one context are appropriate in the context of ME unless someone has done some careful long term monitoring.
With appropriate followup testing, it should be somewhat straightforward to decide on effective treatments to try. I think it's also a bit ridiculous to completely withhold treatment for a severely disabling symptom on the excuse that it might cause unexpected problems.

OI can and has left me bedbound for weeks at a time. Being forced to lie down all day is painful, frustrating, and really really boring. It's well worth trying a reasonable treatment based on trustworthy test results, when that treatment can cause a drastic increase in quality of life.

Indeed, requiring that we KNOW the cause and KNOW exactly how the treatment will and won't effect us is a rather extreme requirement which I don't think is present in any other illness or even idiopathic and uncomplicated cases of OI. And it's that mindset which is leaving us untested and untreated for extremely debilitating symptoms.

Treating my OI has made the biggest difference to my symptoms thus far, and I only wish I was able to do it with active assistance and oversight from a local doctor.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
As I understand it many PWME get orthostatic intolerance. [...] Moreover, symptom relief might go with a long term benefit in some but a long term adverse effect in others. [...] Some of the things I see recommended I would certainly be very wary of - like mineralocorticoid steroids. They may be a godsend to some people but I would not want GPs who do not really understand even the little we understand about ME handing out steroids. The handing out of steroids in rheumatoid arthritis caused a major medical catastrophe for thousands of people.

Very interesting. I have delayed OI (not recognised by my local cardiologist but would get me a diagnosis and treatment in the US). I'm not sure whether to work harder at getting an NHS diagnosis and to seek drug treatment for it, even though it's probably my most limiting symptom. I'm concerned that masking it might hide any improvement I'm getting from things I'm trying that could address the fundamental immune problems, and that using steroids etc. might cause long-term harm, as well as interfering with immune therapies. On the other hand, Prof Newton has just shown that having OI is related to early mortality. Tough one.