Queensland Government: Gold Coast researchers make chronic fatigue breakthrough
- Thread starter Kati
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I am not sure this is still the case. Studies used to go either one way or the other. Now we know they used two different approaches, in serum and out of serum, and only the in serum test is accurate for us.
There's a (2015) review here:
Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity
But more importantly, in the real world, at the Open Medicine Institute (OMI) in California they've been using the same Quest Diagnostics Nichols Institute laboratory* for the past few years and have consistently found either low or low-normal results for natural killer cell function for the majority of ME/CFS patients tested.
I guess the bottom line is that if you have ME/CFS then you're more likely to have lower NK cell function. Some patients do not, though, so it's not diagnostic.
*Select "CA - Focus Diagnostics..." for the lab that OMI uses from the dropdown menu
Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity
But more importantly, in the real world, at the Open Medicine Institute (OMI) in California they've been using the same Quest Diagnostics Nichols Institute laboratory* for the past few years and have consistently found either low or low-normal results for natural killer cell function for the majority of ME/CFS patients tested.
I guess the bottom line is that if you have ME/CFS then you're more likely to have lower NK cell function. Some patients do not, though, so it's not diagnostic.
*Select "CA - Focus Diagnostics..." for the lab that OMI uses from the dropdown menu
I have none handy, but this has been discussed dozens of times here. It was also discussed at the last IACFSME conference if I recall correctly. Maybe someone else can supply a direct reference.
PS Thanks @nandixon
PS Thanks @nandixon
I was thinking of this thread, which includes consideration of that review. In the thread, @Jonathan Edwards reported
and
. (For those who may not pick up on this reference, Nancy Klimas did some of the earliest NK cell studies and has long been associated with this aspect of ME/CFS research.)
As a result, a large international collaborative study has been set up, of which JE is a part, to try to replicate NK cell activity findings.
My point was simply that it cannot be assumed, as do the Griffith researchers, that differences in NK cell activity mean that the differences arise from the cell, particularly not when there is no consensus about whether the differences really exist.
Even if the differences were consistent, they could still arise from the serum that the cells were exposed to before they were isolated and tested. In this case, length of time and nature of treatment between isolation and assay could be a very important variable which might not be recognised and accounted for.
I don't think that's right. There are essentially two types of assays, the original assay based on release of chromium from a target cell (previously labelled with radioactive chromium) after exposure to and lysis by the test NK cells, and newer assays using flow cytometry to detect and quantitate the target cell (previously labelled with a fluorescent dye).
The former are essentially done in research labs and used to be considered the gold standard (not sure if they still are). The latter are used in commercial labs and some research labs (including NCNED).
Neither of these types of assays include patient serum. They all use cells isolated from patient blood, washed and treated in various ways before being mixed with the target cells.
and
. (For those who may not pick up on this reference, Nancy Klimas did some of the earliest NK cell studies and has long been associated with this aspect of ME/CFS research.)
As a result, a large international collaborative study has been set up, of which JE is a part, to try to replicate NK cell activity findings.
My point was simply that it cannot be assumed, as do the Griffith researchers, that differences in NK cell activity mean that the differences arise from the cell, particularly not when there is no consensus about whether the differences really exist.
Even if the differences were consistent, they could still arise from the serum that the cells were exposed to before they were isolated and tested. In this case, length of time and nature of treatment between isolation and assay could be a very important variable which might not be recognised and accounted for.
I don't think that's right. There are essentially two types of assays, the original assay based on release of chromium from a target cell (previously labelled with radioactive chromium) after exposure to and lysis by the test NK cells, and newer assays using flow cytometry to detect and quantitate the target cell (previously labelled with a fluorescent dye).
The former are essentially done in research labs and used to be considered the gold standard (not sure if they still are). The latter are used in commercial labs and some research labs (including NCNED).
Neither of these types of assays include patient serum. They all use cells isolated from patient blood, washed and treated in various ways before being mixed with the target cells.
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This information is from after that thread. Last year is when a lot of it was figured out. Its been discussed at conferences. It does need more validation, and some formal publication, but its not clear that its wrong. Nancy Klimas talked about some of this on one video she was in, but I do not recall which one. The issue is there is nothing stopping the NK cells working outside of our blood. Presumably the shift takes time. I do want to see formal confirmation of this though. It cannot be cited in a scientific paper properly unless its published. Ron Davis is doing work similar to this, but not focused on NK cells. Its also possible this is wrong, but again I would like to see formal confirmation of this in a paper.
In any case I do think there is a high risk of false positives in the NK cell research at NCNED.
In any case I do think there is a high risk of false positives in the NK cell research at NCNED.
At least with respect to the Quest Diagnostics laboratory - the Nichols Institute - that the OMI uses for their natural killer cell function tests, that lab has a very strict protocol for collection, temperature to be maintained during shipping, and maximum time allowed from the time the blood is drawn until received by the lab. The lab must be contacted first before any sample is sent to them and they reject any samples that have deviated from protocol. Whatever it means, NK cell activity is consistently found to be low in most ME/CFS patients under those uniform testing conditions.
So I don't have any problem with that finding from the Griffith researchers. But there are at least a couple of other potential problems.
For one, they only looked at calcium flux with respect to the endoplasmic reticulum (ionomycin can only release calcium from the endoplasmic reticulum). I think they should have done at least a couple of experiments with the addition of other reagents to look at calcium flux from the lysosomes, especially since there may be reduced calcium content and/or release from the lyposomes due to the low sphingolipids that Naviaux found in his metabolomics study.
I find it hard to believe, too, that the TRPM3 SNPs they identified are doing anything more (at most) than exacerbating an existing problem with respect to the NK cells, which very well may include a calcium mobilization problem, but one that is probably at least a little different than what they're envisioning.
So I don't have any problem with that finding from the Griffith researchers. But there are at least a couple of other potential problems.
For one, they only looked at calcium flux with respect to the endoplasmic reticulum (ionomycin can only release calcium from the endoplasmic reticulum). I think they should have done at least a couple of experiments with the addition of other reagents to look at calcium flux from the lysosomes, especially since there may be reduced calcium content and/or release from the lyposomes due to the low sphingolipids that Naviaux found in his metabolomics study.
I find it hard to believe, too, that the TRPM3 SNPs they identified are doing anything more (at most) than exacerbating an existing problem with respect to the NK cells, which very well may include a calcium mobilization problem, but one that is probably at least a little different than what they're envisioning.
The point is that they continue to believe they have identified a problem in TRPM3 (in spite of the FDR and Bonferroni statistical correction results for the SNPs of the immediately prior targeted GAS study), because they write in the current study:
and
The suggestion then is that their current in vitro results are taking precedence and showing there is in fact a problem in TRPM3.
Like I said previously, though, I think any possible problem in TRPM3 is merely exacerbating a different problem(s) with calcium mobilization that they haven't fully elucidated yet.
and
The suggestion then is that their current in vitro results are taking precedence and showing there is in fact a problem in TRPM3.
Like I said previously, though, I think any possible problem in TRPM3 is merely exacerbating a different problem(s) with calcium mobilization that they haven't fully elucidated yet.
I just interpreted that as wishful thinking and rhetoric trying to make a thin observational study seem more significant. Of course they would LIKE there to be something fundamentally wrong and they are trying to manipulate us into thinking the same way. It makes the study look important.
I thought their use of the SNP differences in discussion in the paper and in the recent publicity was just part of this bolstering process - essentially dishonest, but just a rhetorical manipulative device.
I hope they don't REALLY believe it in face of their own research. Would that lead to cognitive dissonance?
I agree.
I thought their use of the SNP differences in discussion in the paper and in the recent publicity was just part of this bolstering process - essentially dishonest, but just a rhetorical manipulative device.
I hope they don't REALLY believe it in face of their own research. Would that lead to cognitive dissonance?
I agree.
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I started writing about ME metabolism back in 1998 in relation to intracellular calcium. I would want to know what the intracellular pH is, and what the intracellular citric acid concentration is. Citric acid is a divalent cation chelator. There are of course many other potential causes.
Exactly, my NK cell numbers, both count and function, were low normal? Certainly not great but above the reference range a bit. I believe my NK cell function number on the Quest Diagnostics test was 33. IIRC. But OMI says I have ME unquestionably due to my symptoms, also a number of autoantibodies against Adrenergic and Muscarinic receptors, something Fluge and Mella found often in their RTX trials.
Thanks Alex,
I see what you mean i.e. an alternative explanation is that there is something in the plasma which is effecting the cells. The recent paper by Chris Armstrong seemed to identify increased levels of certain fatty acids (from memory) it would be interesting to see the different between plasma from people with ME/CFS and healthy controls. Also, presumably as well as a trigger [possibly high levels of something(s) in the plasma] you also need a receptor e.g. TRPM3.
I see what you mean i.e. an alternative explanation is that there is something in the plasma which is effecting the cells. The recent paper by Chris Armstrong seemed to identify increased levels of certain fatty acids (from memory) it would be interesting to see the different between plasma from people with ME/CFS and healthy controls. Also, presumably as well as a trigger [possibly high levels of something(s) in the plasma] you also need a receptor e.g. TRPM3.
Ron Davis claims to have deduced the approximate molecular weight (actually that is my interpretation of what he said) of a possible inhibitory protein in our serum. There is so very much more to do here. We also know of two signalling factors that will have an impact. This research will, I hope, advance fast.
What? Where did he say this?
Okay, "A big molecule", "protein", "A protein complex" is not as specific as Alex was implying. (and a protein/protein complex is what most of us would guess anyway).
In one of his recent videos. Its about the electrical impedance findings. Its also discussed in that thread ... look for the breadbox commentary. When using some kind of filter he was able to refine the size of some kind of molecule, possibly a protein. With a filter of one size there is a problem, of the next size (down, presumably) no problem. This is not formally written up, and I hope he does so at some point. However all this is in the middle of extensive and expanding experiments. Its not over.