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A Preliminary Comparative Assessment of the Role of CD8+T Cells in Chronic Fatigue Syndrome/ Myalgic

JaimeS

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A Preliminary Comparative Assessment of the Role of CD8+T Cells in Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis and Multiple Sclerosis.

Ekua W Brenu1, Simon Broadley3, Thao Nguyen1,2, Samantha Johnston1,2, Sandra Ramos1, Don Staines1, Sonya Marshall- Gradisnik1,2

1The National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Griffith University, Gold Coast, Australia.
2School of Medical Science, Griffith University, Gold Coast, Australia.
3School of Medicine, Griffith University, Gold Coast, Australia.

Abstract
Background CD8+T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

Methods
This preliminary investigation comprised of 23 CFS/ME patients, 11 untreated MS patients and 30 non-fatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+T cells were divided into naïve, central memory (CM), effector memory CD45RA- (EM cells) and effector memory CD45RA+ (EMRA) cells.

Results
Surface expression of BTLA, CD127 and CD49/CD29 were increased on subsets of CD8+T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+T cells in comparison to the non-fatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the non-fatigued controls.

Conclusions
The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings.

Full article attached; it's via Google Scholar, but I have no idea where the original file was posted. I definitely got it for free, though. Please let me know if posting it in its entirety here is inappropriate! :)

-J
 

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heapsreal

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@JaimeS
Thanks for posting this.

I know griffith university were looking at doing a study on nk function, nk bright and dim cells comparing cfs/me with ms and healthy controls, do you know if they have done this study??
 

Simon

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These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings.
This gets my applause for a very reasonable and helpful conclusion that we need to see far more often.

Too many studies (not just mecfs) conclude there is yet another (promising) biomarker, and are never heard of again.

I know there are many pressures on researchers to hype their results, not least the need to secure grants/their jobs, but hype doesn't help progress and probably impedes it where it's championing blind alleys.
 
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Marky90

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What do you make of this @Jonathan Edwards ? I know T-cells seldom get invited for a cup of tea with you, but is there potentially anything here (a larger sample size is obviously needed..)
 

Jonathan Edwards

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What do you make of this @Jonathan Edwards ? I know T-cells seldom get invited for a cup of tea with you, but is there potentially anything here (a larger sample size is obviously needed..)

Any difference in lymphocyte subset profile in ME/CFS would be of interest and it will be interesting to see if this can be replicated. A subgroup of ME.CFS patients may have CD8 T cell medicated disease. I am not sure how MS fits in to the study other than as s disease control. I am not personally convinced that CD8 T cells have much to do with MS.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
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Any difference in lymphocyte subset profile in ME/CFS would be of interest and it will be interesting to see if this can be replicated. A subgroup of ME.CFS patients may have CD8 T cell medicated disease. I am not sure how MS fits in to the study other than as s disease control. I am not personally convinced that CD8 T cells have much to do with MS.

Gotcha! I agree that it`s of the essence to try to get a gist of possible subsets (and your thread "Does ME`s cause CFS(?), is so great in that regard ). You mentioned a monoclonal antibody that aims to wash out all t-cells before. Something beginning with the letter C? What`s the risk profile related to this, and if not too high, would it not help to narrow the research in ME/CFS down, if such a study showed that t-cells are probably not involved?
 

Jonathan Edwards

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Gotcha! I agree that it`s of the essence to try to get a gist of possible subsets (and your thread "Does ME`s cause CFS(?), is so great in that regard ). You mentioned a monoclonal antibody that aims to wash out all t-cells before. Something beginning with the letter C? What`s the risk profile related to this, and if not too high, would it not help to narrow the research in ME/CFS down, if such a study showed that t-cells are probably not involved?

Anti-CD52 kills more or less all T cells. Surprisingly, even if people are left with hardly any T cells for years there seem to be few problems. An anti-CD8 could potentially kill just CD8 T cells, and I have always thoughts this would be worth trying in psoriasis or spondarthritis. The authors of this thread study suggest that CD8 are defective, which might suggest that they should not be made even more defective. However, I am not sure that their findings indicate a defect so much as just a difference - which might actually reflect overactivity. Unfortunately, I suspect that nobody is going to design an anti-CD8 antibody because they think it will lead to infection - desite the fact that anti-CD52 does not seem to.
 

MeSci

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Any difference in lymphocyte subset profile in ME/CFS would be of interest and it will be interesting to see if this can be replicated. A subgroup of ME.CFS patients may have CD8 T cell medicated disease. I am not sure how MS fits in to the study other than as s disease control. I am not personally convinced that CD8 T cells have much to do with MS.
I'm guessing that 'medicated' should be 'mediated' - is that right, @Jonathan Edwards?
 

A.B.

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Is there anything interesting about CD127 and PSGL-1?

Wikipedia says CD127 is one of the two protein chains that make up the interleukin 7 receptor.

PSGL-1 helps white blood cells stick to the endothelium of blood vessels so that they can reach inflamed tissues.

Both of these findings seems more related to weaker immune system function.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
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Anti-CD52 kills more or less all T cells. Surprisingly, even if people are left with hardly any T cells for years there seem to be few problems. An anti-CD8 could potentially kill just CD8 T cells, and I have always thoughts this would be worth trying in psoriasis or spondarthritis. The authors of this thread study suggest that CD8 are defective, which might suggest that they should not be made even more defective. However, I am not sure that their findings indicate a defect so much as just a difference - which might actually reflect overactivity. Unfortunately, I suspect that nobody is going to design an anti-CD8 antibody because they think it will lead to infection - desite the fact that anti-CD52 does not seem to.

Oh really, that`s kind of crazy. I thought T-cells were essential for the innate immune system?

Are you saying that potentially, an anti-cd8 could make ME worse? Could the different cd8-profile be due to an adaption for a autoimmune process?

I`m just asking without the necessary knowledge, sry :p
 
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Gotcha! I agree that it`s of the essence to try to get a gist of possible subsets (and your thread "Does ME`s cause CFS(?), is so great in that regard ). You mentioned a monoclonal antibody that aims to wash out all t-cells before. Something beginning with the letter C? What`s the risk profile related to this, and if not too high, would it not help to narrow the research in ME/CFS down, if such a study showed that t-cells are probably not involved?

Campath ? (Alemtuzumab)
 

Jonathan Edwards

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Oh really, that`s kind of crazy. I thought T-cells were essential for the innate immune system?

Are you saying that potentially, an anti-cd8 could make ME worse? Could the different cd8-profile be due to an adaption for a autoimmune process?

I`m just asking without the necessary knowledge, sry :p

T cells are generally thought to be essential for the adaptive immune system (the aspect that recognises specific antigens). In AIDS very low CD4 T cell levels lead to opportunistic infection. However HIV does more than just lower T cel levels. It screws up cellular interactions in other ways. The surprising finding with anti-CD52=campath1H was that although it drastically lowers t cell levels this does not produce major issues with infection. It is also of note that it does not seem to produce symptoms like ME/CFS.

That is one of the reasons why the more I think about it the less likely it seems that ME/CFS has anything to do with immunodeficiency. Serious immunodeficiency does not produce ME/CFS type symptoms, even if there are viral infections as I understand it. ME/CFS seems to be a problem that can follow infections but does not look like the efect of active infections.

So I doubt anti-CD8 would be likely to make ME/CFS worse. If CD8 T cells are relevant to ME/CFS I would expect that to be due to overactivity - analogous to the B cell overactivity in autoimmune disease.
 
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Yes! Thanks BurnA

Very Interesting story about the development of Campath1H here

Intro :

The unfortunate reality is that clinical development of new drugs is almost entirely in the hands of the pharmaceutical industry, where many factors other than strictly scientific/clinical ones influence the decision to develop a particular product. These include the availability of patent protection, the potential size of the market, the impact of new drug regulations and the current mood of investors. Profitability is the over-riding concern and is an essential ingredient of success in our society. However, we do not think it is enough for academic scientists to patent a new technology, license it on to industry and sit back with large up-front payments. Physicians and their patients are cut out of the decision process and become essentially a commodity to be bought or discarded during the clinical trials. A better way is for scientists, physicians, patients, industry and government to work together, each recognising the different priorities of the other, but each contributing to the decision process. Biological therapies will be costly and they do carry risks of introducing dangerous new diseases. We all have an interest in their effective application.

Here we will tell the story of CAMPATH-1, just one of many hundreds of monoclonal antibodies developed for therapy. It illustrates several aspects of practical development which might apply to other projects and perhaps the reader will be able to avoid the pitfalls which we encountered. CAMPATH-1 was one of the first therapeutic monoclonals to be assigned for commercial development and it was licensed to one of the best equipped UK Biotech companies of the time. However, were it not for the dedication of teams of clinicians worldwide who continued to pursue independent trials with our academic group, we are convinced that it would by now have disappeared without trace.
 
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JaimeS

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I think the use of MS controls has more to do with "creative grant accounting", a specialised branch of science that many young scientists now have to master to keep their research afloat.

Exactly. I think that MS and ME have some similarities, which can mean that research for one might lead to interesting insights about the other.

But mainly this is probably due to the fact that research on MS is easier to fund.

-J
 

heapsreal

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Exactly. I think that MS and ME have some similarities, which can mean that research for one might lead to interesting insights about the other.

But mainly this is probably due to the fact that research on MS is easier to fund.

-J


My understanding was they planned to do comparison studies with other neuro immune disease such as ms, parkinsons etc to try and find a diagnostic test which is unique to cfsme.

Partly why they looked further into nk function and persued nk bright and nk dim cells.
 

heapsreal

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Cd8 t cells are also commonly elevated in herpes viruses like ebv and cmv. Ebv is commonly associated with MS, i guess with ebv associated with many in cfsme, it makes sense to compare these 2.

So an elevated cd8 count could indicate a chronic ebv infection, used in conjunction with ebv titre levels. Also a low nk function would make it easier for these infections to reactivate which has been shown in alot of research by klimas, peterson and lerner.

Also both illnesses, cfsme and ms, are commonly misdiagnosed for the other.