Immune and hemorheological changes in Chronic Fatigue Syndrome

[DysautonomiaXMRV]

'Immune and hemorheological changes in Chronic Fatigue Syndrome'

Ekua Brenu, Donald Staines, Oguz Baskurt, Kevin Ashton, Sandra Ramos,
Rhys Christy, Sonya Marshall-Gradisnik
Journal of Translational Medicine 2010, 8:1
http://www.translational-medicine.com/content/8/1/1


Background

Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that
affects various physiological systems including immune and
neurological systems. The immune system has been substantially
examined in CFS with equivocal results, however, little is known about
the role of neutrophils and natural killer (NK) phenotypes in the
pathomechanism of this disorder. Additionally, the role of erythrocyte
rheological characteristics in CFS has not been fully expounded. The
objective of this present study was to determine deficiencies in
lymphocyte function and erythrocyte rheology in CFS patients.

Methods

Flow cytometric measurements were performed for neutrophil function,
lymphocyte numbers, NK phenotypes (CD56dimCD16+ and CD56brightCD16-)
and NK cytotoxic activity. Erythrocyte aggregation, deformability and
fibrinogen levels were also assessed.

Results

CFS patients (n = 10) had significant decreases in neutrophil
respiratory burst, NK cytotoxic activity and CD56brightCD16- NK
phenotypes in comparison to healthy controls (n = 10). However,
hemorheological characteristics, aggregation, deformability and
fibrinogen, lymphocyte numbers and CD56dimCD16+ NK cells were similar
between groups.

Conclusion

Immune dysfunction may therefore be an important contributory factor
to the mechanism of CFS, as indicated by decreases in neutrophil
respiratory burst, NK cell activity and NK phenotypes. Thus, immune
cell function and phenotypes are possible diagnostic markers for CFS.

 

[kurt]

That is a great study, thanks for the link, good reading.

What caught my attention was that the cytotoxicity of the NK cells was approximately one third of normal. That is huge and means our NK cells are simply too weak to kill all but the weakest viruses. So of course we have higher viral load.

Here is the result of the cytotoxic study:

Decreased NK cytotoxic activity
NK cytotoxic activity was measured by assessing the ability of NK lymphocytes from the healthy subjects and the control group to induce apoptosis in K562. The percentage lysis for the healthy subjects and the CFS patients were significantly different. After 4 hours of incubation, NK cytotoxic activity was significantly lower in CFS patients compared to the healthy controls (13.6% 5.1 and 34.3% 6.6 SD, respectively, P<0.05). There were more viable cells (Annexin V-FITC negative/ 7-AAD negative) in the patient sample compared to the healthy control group.

All I can say is WOW, this is a smoking gun for CFIDS. So in CFS our NK cells are only about 40% as deadly in their attacks on pathogens as normal NK cells (13.6%/34.3%=39.7%).

From the conclusion of the paper:

Conclusions
The information presented in this study confirms significant declines in immune function in CFS specifically in CD56(bright), CD16- NK cell numbers, NK cytotoxicity and neutrophil respiratory burst. This is the first study to simultaneously assess innate immune function, phagocytosis and cytotoxic activity in CFS. The defects in innate immune function observed in this study potentially suggests an altered adaptive immune response in CFS and these may be important in understanding the pathomechanism of CFS. Further studies are however required to determine cytokine and chemokine ...

If CFS were funded normally as a regular disease should be, this study would be quickly replicated with a larger 'N' (this was only N=10). So PWC appear to have an altered adaptive immune response.

 

[fresh_eyes]

So in CFS our NK cells are only about 40% as deadly as normal NK cells (13.6%/34.3%=39.7%).

Kurt, thanks so much for putting this in terms I can understand! Wow indeed.

 

[Athene]

Kenny De Meirleir did these tests on me - as far as I know he does on all his patients. My results were like those described in the paper. I think he must have a vast amount of patient data on this. I find it hard to find his research online but I wonder if he has published anything on this?

BTW dysautonomia, thank you for all your posts. You constantly bring up very interesting and informative topics and I really appreciate your contribution here.

 

[fairlight]

dysautonomia-

I think that CFS is an immune disorder that we are predisposed to and wil have to be treated as a disease of the immune system. This is why people have had good results with rituxan, methotrexate and stem cell transpalnts. I don't think anti-virals are the answer for many of the cases . (Just my opinion).

Thanks for posting this study.

 

[Countrygirl]

That is a great study, thanks for the link, good reading.

What caught my attention was that the cytotoxicity of the NK cells was approximately one third of normal. That is huge and means our NK cells are simply too weak to kill all but the weakest viruses. So of course we have higher viral load.

All I can say is WOW, this is a smoking gun for CFIDS. So in CFS our NK cells are only about 40% as deadly in their attacks on pathogens as normal NK cells (13.6%/

Hi Kurt,

I wonder if you could possibly answer a question I've just posted somewhere else. A number of us never develop minor viral infections after developing M.E. I haven't had a cold since I became ill 30 years ago, whereas, before, I seemed to catch every bug in the neighbourhood and took an age to not quite shake them off. Now, if there is a heavy duty virus doing the rounds, say a flu bug, I do develop the infection, but can't run a proper fever. My question is this: how come the immune system seems to have an unnatural ability to blat a minor virus at 50 paces, but can't fight a more serious one?

My consultant says a number of his ME patients also do not develop cold symptoms anymore. How come, when our immune system is damaged? Perhaps the word should be dysregulated rather than just damaged as one part seems really up-regulated. Could it be that our immune system just can't produce the symptoms of an infection ?

Thanks to anyone who can have a shot at answering this.

Best wishes,

C.G.

 

[Gerwyn]

With the HPA axis depressed,as found in many studies,the immune system is permanently switched on to a lesser or greater degree----I know i did,t catch anything for years now I,m better I catch practically everything.Dr Myhill provides a better and more detailed explanation than me.

 

[Countrygirl]

43059]With the HPA axis depressed,as found in many studies,the immune system is permanently switched on to a lesser or greater degree----I know i did,t catch anything for years now I,m better I catch practically everything.Dr Myhill provides a better and more detailed explanation than me.

Thank you Gerwyn. I'm still puzzled though. Does it mean that our feeble, much-reduced NK cells are just being flogged to death ? They must be knackered!

So it sounds like a chicken-and-egg scenario here: which came first - the virus or the depression of the HPA ?

Can someone remind me, if we ever knew, how XMRV can cause the HPA dysfunction?

Thanks.

Brain dead.

 

[thefreeprisoner]

Hi Countrygirl,

My question is this: how come the immune system seems to have an unnatural ability to blat a minor virus at 50 paces, but can't fight a more serious one?

I was under the impression that some cold symptoms are actually by-products of your body responding to the virus. Runny nose for example - that's your body kicking out the dead virus bits being swept up from your throat and lungs, right? (Spoken like a true non-scientist.) So if your body were unable to fight a cold it would just contribute to your general feeling of ill-health rather than manifesting itself as a true cold. But I could be completely wrong about that -- somebody please enlighten me!

My consultant says a number of his ME patients also do not develop cold symptoms anymore. How come, when our immune system is damaged? Perhaps the word should be dysregulated rather than just damaged as one part seems really up-regulated. Could it be that our immune system just can't produce the symptoms of an infection ?

I'd be wary of relying on anecdotal evidence as supporting / not supporting any theory. If there's a research paper which investigates whether M.E. patients catch colds less frequently, I'd be very interested to see it. I have caught a cold since contracting M.E. and it completely undid my recovery - I was bed-bound again. However, before my second relapse on October last year, I seldom caught colds.

Rachel xx

 

[Dolphin]

I just read this and found it interesting.

Note: I think the references go off somewhere around 12/13 and that [x] refers to x+1 in the references for a lot of the paper. I have just written to the corresponding author to tell them.

Looking at Figure 4, it is surprising that there is no statistically significant difference between them. I think a larger sample might have found a difference.
This is to do with Les Simpson's work. I had an abnormal test with him before (I would need to check it to see which type).

 

[Dolphin]

I just read this and found it interesting.

Note: I think the references go off somewhere around 12/13 and that [x] refers to x+1 in the references for a lot of the paper. I have just written to the corresponding author to tell them.

Here's what I wrote to them in case anyone is wondering:

Thank you for doing this interesting research.

Unfortunately, some of the references don't match up.
For example,
"Data from gene expression studies in CFS have indicated differential expression in the chemokine receptor CXCR4 [30]," - should match with this:

31. Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey Dl, Richards SC, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J, Enlander D, Nutt DJ, Holgate ST: Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis 2008, 197:1171-1184.

And

"Moreover, phagocytes such as neutrophils have received little attention, only one study has revealed that neutrophils in CFS are more prone to apoptosis, this was heightened by the existence of large quantities of TGFb1[12]."

and

"High levels of TFG-b
also cause an increase in neutrophil apoptosis and this occurs in some cases of CFS [11]."

I think refers to:

13. Kennedy G, Spence V, Underwood C, Belch JJF: Increased neutrophil apoptosis in chronic fatigue syndrome. J Clin Pathol 2004, 57:891-893.

This is an online journal so one should be able to upload a version with the correct numbering, I reckon.


I am not definite but I think most or all from around 13-31 (and perhaps a bit more) are one off i.e. [x] in text refers to x+1 in references.

They said they were going to fix it but 2.5 years later, it hasn't been done. Not the end of the world of course.