Longitudinal investigation of natural killer cells and cytokines in CFS/ME

[Ember]

Author: Ekua W BrenuMieke L van DrielDonald R StainesKevin J AshtonSharni L HardcastleJames KeaneLotti TajouriDaniel PetersonSandra B RamosSonya M Marshall-Gradisnik

Credits/Source: Journal of Translational Medicine 2012, 10:88

Published on: 2012-05-09

http://7thspace.com/headlines/41204...atigue_syndromemyalgic_encephalomyelitis.html

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time.

This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+) and cytokines, over the course of a12 month period in patients with CFS/ME.

Methods: The participants in the study comprised 65 (47.2+/-11.5 years) CFS/ME participants and 21 (45.2 +/-9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3).

Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells.

Results: NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2.

Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-gamma and TNF-alpha at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non- fatigued controls.

Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to the T1 and T3.

IL-10 and IL-17A secretion was elevated at T2 in comparison to the T1 and T3.

Conclusion: These results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study (emphasis added).

 

[nanonug]

Awesome find! This is something that can actually be objectively tested. And no talk of neurological disease!

EDIT - Found a link to a provisional PDF:

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis

A link to the "final" PDF will be probably be found here:
http://www.translational-medicine.com/content/10/1/88/abstract

 

[SOC]

Three cheers for Bond Uni!

This is more great (?) news on the immune front, clearly demonstrating an important difference in immune function between patients and controls. Explain that one, biopsychosocial people!

If this results in a biomarker, I may find myself kicked out of the diagnosis since, at least at the time my immune tests were done, my NK cell number and function were fine. My bugaboo look like low cytotoxic T cells (among other things). Maybe I'll get my own diagnosis with it's own special acronym.

I'm not sure what to make of the changes over time in all those cytokines and whatnot. That they are substantially different from the controls, I understand, but the pattern of fluctuation being consistent among patients seems weird. Maybe it will be clearer when the graphs and figures are available.

 

[August59]

Dr. Montoya has stated that it is probably going to go back to the inate immune system and I believe this at least partially bears this out. My concern is how in the world could you possibbly ever treat such a widely malfunctioning system in the body. This may be where Ampligen has it's place or eventually a newer version of Ampligen. And then try to somehow suppress or rid our bodies of all of the pathogens we have going on. What was a little concerning was the immune system seemed to be completely different at 0 - 6 - 12 months, so where is it at 24 months?

It has been a long road getting here, so I imagine it will be a long road to home, if that's ever possible.

Can anyone take anything from this study to conclude what may be some things we should be doing or not be doing? I know that is a loaded question, but just opinions is what I was getting at. Thanks

 

[kurt]

I can hardly believe this is the first longitudinal study of NK function given how long this problem has been known. But great to see this at long last.

Can anyone take anything from this study to conclude what may be some things we should be doing or not be doing? I know that is a loaded question, but just opinions is what I was getting at. Thanks

This would seem to support the use of GcMAF, or maybe the homeopathic KMAF, and perhaps some natural NK-boosting formulas (mushroom extracts, etc). However, I don't know whether those measures are enough to boost cytotoxicity, or if they just increase cell counts.

Also, my conclusion is that this is indirect evidence of a viral problem, as low NK cytotoxicity means we are not as capable of removing viral-infected cells. Therefore, treatment use of antivirals, pharmaceutical or natural, would seem indicated by this study.

Another interesting correlation with a known CFS treatment is that studies have shown that Rituximab can alter NK cell cytotoxicity and expression, although there are so many studies, I have not been able to find a good explanation to share. But there is definitely a lot of research into the interaction between NK cells and Rituximab.

 

[nanonug]

Can anyone take anything from this study to conclude what may be some things we should be doing or not be doing?

Maybe this:

Resveratrol enhances perforin expression and NK cell cytotoxicity through NKG2D-dependent pathways

If you do a search on Pubmed for "nk cell cytotoxicity", you get a bunch of results. Some of them might be useful...

 

[kurt]

Here is an interesting quote from the provisional article:

The exact consequence of alterations in CD5[bright] CD16- NK cells in CFS/ME is not fully known, however, patterns of CD56[bright] CD16- NK cells were affected by seasonal changes which may affect NK cytokine production. Incidentally gene expression of IFNG which is an important NK cytokine was significantly decreased in the NK cells of CFS/ME patients [25], which may be related to the decrease in CD56[bright] CD16- NK cells. Decreases in CD56[bright] CD16- NK cells have been observed in coronary heart disease, allergic rhinitis and juvenile rheumatoid arthritis while in diseases such as Chronic Obstructive Pulmonary Disease (COPD) CD56[bright] CD16- NK cells have been reported to be increased [39,40].

So does this suggest that at least the immune dysfunctional part of CFS may have some 'relatives' ? Would be nice to belong to some known group of diseases. Maybe there are some other common factors, and treatments that could be shared, at least for the known immune component.

 

[alex3619]

If this results in a biomarker, I may find myself kicked out of the diagnosis since, at least at the time my immune tests were done, my NK cell number and function were fine. My bugaboo look like low cytotoxic T cells (among other things).

Hi SOC you could be right about this but then again its not necessarily regular NK function or numbers that appear to be the predominant marker, but the ratio of bright to dim cells. Bright cells are NK cells that have been fully activated - on duty as it were. Most NK cell function tests may be looking at combined function rather than bright cell function. When this test is improved, expect to see our views changing, because this could be a major step forward. However this will not be a simple or cheap test using the tech I am familiar with: the NK cells have to be stained and then examined. This means people or expensive machines.

Bye, Alex

 

[nanonug]

However this will not be a simple or cheap test using the tech I am familiar with: the NK cells have to be stained and then examined. This means people or expensive machines

I sent Metametrix an email suggesting they develop such a test. It would be nice to actually have something like this widely available.

 

[August59]

Here is an interesting quote from the provisional article:



So does this suggest that at least the immune dysfunctional part of CFS may have some 'relatives' ? Would be nice to belong to some known group of diseases. Maybe there are some other common factors, and treatments that could be shared, at least for the known immune component.

Good catch! Thanks for the feed back because quite honestly as long as I have been on this forum I can't put all of this NK, cytokine, CD bright and misc. together. It's my CFS ADD I suppose. It does seem to point to supporting Immune function(?), keeping oxidative stress as low as possible and fight the pathogens as smart as we can. I'm going to be real interested to see what Dr. Montoya's pathogen study reveals. I'm sure there are going to be many that we should be checked for and very, very few of us that have been checked for these pathogens. EBV, HIV, HHV6 & CMV are the only things I have been checked for and these are all viruses. I've never been checked (I should be saying tested) for any type of bacteria type pathogens except for an ELISA Lyme test 6 months after the tick bite.

I was also surprised that it seems not many people were aware of this study and the numbers, although not large, are far better than some the studies I've seen get published.

I also have a gut feeling Dr. Montoya and Dr. Lipkin feel that there is a very significant, but unproven malfunction of the immune system or an undiscovered pathogenic process taking place and that it will have more far reaching implications than just ME/CFS. It just appears to me that they are not sand bagging at all and are very interested in where there studies are going to take them. More studies, funding and a chance to put their name on what quite possibly be a ground breaking discovery. This is good for us and others! I hope!

 

[heapsreal]

My blood was apart of that study and yes my nk function test was low and my nk bright cells were low too. I have posted this before but i believe dr peterson is teaming up with the bond group who are now moving to a bigger and maybe better funded university in australia. They will be doing a study comparing nk function and bright cells etc with MS and rheumatoid arthritis people.

cheers!!!

 

[hixxy]

My blood was apart of that study and yes my nk function test was low and my nk bright cells were low too. I have posted this before but i believe dr peterson is teaming up with the bond group who are now moving to a bigger and maybe better funded university in australia. They will be doing a study comparing nk function and bright cells etc with MS and rheumatoid arthritis people.

cheers!!!

That would be a good group to be bundled with. Lots more funding.

Obviously I've never been able to have this NK function test done, but the only basic cytokine panel I had done had elevated IL-10. Don't know how significant this is on it's own.

 

[hixxy]

Full provisional submission in PDF format at: http://www.translational-medicine.com/content/pdf/1479-5876-10-88.pdf (Transitional Medicine Journal)

 

[ukxmrv]

Heaps,

Thanks for volunterring to be a patient in that study!

Do you know if there is an email address or anything for the Bond group to volunteer for future studies?

 

[heapsreal]

we never got our cytokine results though only the nk results. I might email them about this. My nk numbers i get done through my normal doc have always been within the normal range but that doesnt mean alot if they dont work. I have also had a lymphocyte function test in the past and it came back normal, but again it wasnt specific to nk cells.
It would be interesting to see if nk function is the cause or just an effect of cfs??

cheers!!!

 

[heapsreal]

Heaps,

Thanks for volunterring to be a patient in that study!

Do you know if there is an email address or anything for the Bond group to volunteer for future studies?

Not sure where u live but they only seem to be taking people who live in the brisbane and gold coast areas. The studies are usually more then 1 blood test eg every 6 months over 18 month period was the last study. jparkes@bond.edu.au Jillian is the lady who was emailing us and organising alot to do with the study, she would be the one to email about being involved in future studies.

cheers!!!

 

[hixxy]

Even if it only has the flow on effect of the disease being taken seriously and possibly the development of a biomarker, the work at Bond is worth every penny and then some. :victory:

If the disease can finally be 100% proven to be immune in origin, then immunologists and neuroimmunlogists will have to pull their shit together.

 

[ukxmrv]

I don't know if it is the case in Australia but in the UK my own private similar immune function tests were completely disregarded by NHS doctors are not being "meaningful" and almost derided as "experimental".

So impressed by the Bond group and hoping for you all that these studies will be taken seriously.

(thanks Heapsreal for the email address. I have a relative in that area who may be able to take part).

 

[alex3619]

My blood was apart of that study and yes my nk function test was low and my nk bright cells were low too. I have posted this before but i believe dr peterson is teaming up with the bond group who are now moving to a bigger and maybe better funded university in australia. They will be doing a study comparing nk function and bright cells etc with MS and rheumatoid arthritis people.

cheers!!!

Hi heapsreal, Such a study is exactly what I have been looking for. Indeed a blog I intend to post in a couple of days (after the forum moves) calls for an MS and ME comparison - maybe I should link to your post? Bye, Alex

 

[hixxy]

I don't know if it is the case in Australia but in the UK my own private similar immune function tests were completely disregarded by NHS doctors are not being "meaningful" and almost derided as "experimental".

So impressed by the Bond group and hoping for you all that these studies will be taken seriously.

(thanks Heapsreal for the email address. I have a relative in that area who may be able to take part).

All tests and discoveries in medicine were once experimental. I wonder what it takes for a test to go from experimental to meaningful? Money in their pockets?