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German study finds xmrv

lansbergen

Senior Member
Messages
2,512
Gerwyn -- thanks for making this clarification. So many have described ME/CFS (or whatever you want to call it) as a result of a suppressed immune system. It's my understanding that the the top docs and studies have shown the immune system is dysregulated / imbalanced (a Th1/Th2 imbalance) / or modulated, as you say.

I agree with you.

I use an immunemodulator that is supposed to be able to restore Th1/Th2 balans. It saved my live and it is still helpfull. When I forget to take it, I will notice the following day.
 

guest

Guest
Messages
320
Thanks awol, I completely agree. HIV does not cause immune suppression, it causes immune dysfunction. In my eyes this is what is going on with most PWCs, our immune system is not suppressed but it is completely out of balance.
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
Saying with one sweeping statement that retroviruses cause immune suppression is premature in the case of xmrv because we don't know exactly what it does to the immune sytem yet. Normally, when you have a viral infection, the immune system is ACTIVATED, not suppressed. However xmrv may be causing changes to our immune systems that make the normal immune response ineffective, even while active. This is dysfunction, not suppression.

You are right, I took "suppression" to be synonymous with "deficiency", but actually the correct term is deficiency. I'm fine with the word immunodeficiency. The quote I was thinking of is actually this one using the term immunodeficiency:

http://www.nimr.mrc.ac.uk/virology/bishop/

Retroviruses cause severe diseases, including immunodeficiency and cancer. The human immunodeficiency virus (HIV) is the most widely known retrovirus due to its impact on human health.
 
G

Gerwyn

Guest
I agree with you.

I use an immunemodulator that is supposed to be able to restore Th1/Th2 balans. It saved my live and it is still helpfull. When I forget to take it, I will notice the following day.

would you mind telling me which one it is please?
 

Megan

Senior Member
Messages
233
Location
Australia
Thanks Gerwyn and Dr Yes for responding to my queries on the methodology in this study. I find these forums helpful in following things as I don't have a scientific background, though I am a keen reader of all of the papers. I have another query regarding the current German paper. I find the following quote ambiguous:

"All samples that were positive for XMRV by gag-nested PCR, together with a set of those that were negative for XMRV, were retested by real-time PCR. Results showed low XMRV RNA concentrations, 103 –104/mL of specimen."

It sounds like the 'negative' nested PCR cases tested positive using real-time PCR too? Or surely they would have said that the negative cases tested negative, or that the tests correlated? If so why haven't they said how many 'negative' cases were tested in this way? Was their first round of nested PCR testing giving false negatives? Are they really suggesting that the virus may actually present in way more people, but perhaps is just more readily detectable in some?

I would like to think that I am reading this wrong, but I find it hard to read without thinking they need to have explained more here.
 
D

DysautonomiaXMRV

Guest
Question:
What constitues immune supression?
Immunosuppression involves an act that reduces the activation or efficacy of the immune system.

Question:
What is that 'act' of immune supression in ME CFS - if at all?

Hypothesis:
The act may be greatly impaired NKC function - due to cells being permanantly infected with XMRV.
This would provide evidence of immune supression by lowering of defensive measures of the innate immune system to defeat viruses.
(NB: Infection of T-Cells and B-Cells with XMRV has already been demonstrated, not postulated).

Future Research coming on ME CFS:
XMRV infects NKC cells in patients with ME CFS.

Existing Research known:
NKC cells use a protein, perforin, to enable targeting of cells and perforin helps to complete apoptosis (killing target cells) . Levels of perforin are lowered in ME CFS, reducing abilty of NKC cells to function. Now see above on XMRV infecting NKC cells and it all potentially begins to make sense.

In my opinion (not fact), this could mean ME CFS patients infected with XMRV, could indeed have a subtle form of immune supression previously undetected due to NKC function only being assessed in patients with ME CFS on a research basis, and XMRV's actions being unknown due to it's discovery in ME CFS only in 2009. :Retro redface:
 

awol

Senior Member
Messages
417
Immunosuppression involves an act that reduces the activation or efficacy of the immune system

Question:
What is that 'act' in ME CFS?

Hypothesis:
The act may be greatly impaired NKC function - due to cells being permanantly infected with XMR.
This would provide evidence of immune supression by lowering of defensive measures of the innate immune system to defeat viruses.

Future Research coming on ME CFS:
XMRV infects NKC cells in patients with ME CFS.

Existing Research known:
NKC cells use a protein, perforin, to enable targeting of cells and perforin helps to complete apoptosis (killing target cells) . Levels of perforin are lowered in ME CFS, reducing abilty of NKC cells to function. Now see above on XMRV infecting NKC cells and it all potentially begins to make sense.

In my opinion (not fact), this could mean ME CFS patients infected with XMRV, could indeed have a subtle form of immune supression previously undetected due to NKC function only being assessed in patients with ME CFS on a research basis, and XMRV's actions being unknown due to it's discovery in ME CFS only in 2009. :Retro redface:

I am not trying to be a pest, but mixing up suppression, deficiency and dysfunction is causing A LOT of confusion here. In your definition above "act" is exactly that. It is either the choice to engage in activities that are intense and therefore put the immune system on the back burner, or the deliberate administration of steroids and medications to block the immune system. Depression also raises cortisol which suppresses the immune system.

NK abnormalities are DYSFUNCTION not suppression.
 

awol

Senior Member
Messages
417
The reason this distinction is EXTREMELY important here is that the paper dealt with a group of people whose immune systems WERE suppressed. This is done DELIBERATELY to transplant patients because otherwise their new organs would be rejected as foreign objects.
 

shannah

Senior Member
Messages
1,429
Lansbergen,

If it's not too much bother, I'd love to know what you're using as well.

Thanks
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
I am not trying to be a pest, but mixing up suppression, deficiency and dysfunction is causing A LOT of confusion here. In your definition above "act" is exactly that. It is either the choice to engage in activities that are intense and therefore put the immune system on the back burner, or the deliberate administration of steroids and medications to block the immune system. Depression also raises cortisol which suppresses the immune system.

NK abnormalities are DYSFUNCTION not suppression.

There actually doesn't seem to be a clear-cut medical distinction between immune "suppression" and immune "deficiency".

For example:
http://en.wikipedia.org/wiki/Immunosuppression
Immunosuppression is a common aim of many bacterial virulence factors

So in other words according to wiki, pathogens (like xmrv presumably) can cause Immunosuppression.

I'm all in favour of using definitions correctly, but only where there exists a clear definition in the first place.
 

awol

Senior Member
Messages
417
yes I noticed some confusion in online references too, you are right.

Still, it is important for this discussion because the paper was about transplant patients. If we mix up our issues with what is going on in transplant patients and use the same terms no one will understand anything. I am quite sure the distinction actually does exist, but online references can be unreliable.
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
yes I noticed some confusion in online references too, you are right.

Still, it is important for this discussion because the paper was about transplant patients. If we mix up our issues with what is going on in transplant patients and use the same terms no one will understand anything. I am quite sure the distinction actually does exist, but online references can be unreliable.

It would be nice if there was a formal distinction. If you can find some supporting references I'm sure people will respect that.
 

awol

Senior Member
Messages
417
It would be nice if there was a formal distinction. If you can find some supporting references I'm sure people will respect that.

I actually think that Dysautonomia's definition above supports this distinction. An "act" is not the same as a "characteristic" or a "process". HIV is stands for Human immunodeficiency virus, not human immunosuppression virus.

Deficiency is a characteristic
Supression is an action
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
immune suppression, dysfunction and deficiency

I am not convinced that the terms suppression, dysfunction or deficiency have any precise meaning, they are simply shorthand for talking about something which it is presumed you understand. In HIV, you have T cell dysfunction and deficiency, both simultaneously. A strong case can be made for there being suppression and dysfunction and deficiency in CFS. The Th2 arm of the immune system is dysfunctional via being hyperactivated without a clear target. The NK cells are both suppressed and deficient. These are really just buzz words, however, and do not substitute for an understanding of the underlying molecular mechanisms. The problem is that we do not yet fully understand the molecular mechanisms of CFS and ME, so everyone uses buzzwords. Don't get hung up on them, focus on the facts and those mechanisms we understand.

Here is a conundrum you might like to think about, that in my opinion goes to the heart of science:

Opinion doesn't matter, only the facts.
Facts have to be interpreted.
Interpretation is opinion.

Bye
Alex
 

awol

Senior Member
Messages
417
Here is a conundrum you might like to think about, that in my opinion goes to the heart of science:

Opinion doesn't matter, only the facts.
Facts have to be interpreted.
Interpretation is opinion.

Bye
Alex

Alex I like this quote, thanks.

Still I think the reason for this debate is being lost and this is not helpful. Many people earlier in this thread were having trouble interpreting the german paper, topic of thread, because of the fuzzy understanding of the group of patients with suppressed immune systems that were being studied. In this case, suppression clearly means what I have described. Deficiencies and dysfunctions as we experience them are something else. People need to understand this. That is why the terminology is important.

Following above logic, it is the stated OPINION of some on this thread that jumbled terminology is a matter of opinion. However different words usually exist for a reason. In my humble opinion, it would do a great deal to improve the clarity of this and future discussions if we understand that immune suppression is a normal process that does not imply disease (as in the marathon runner) while immune deficiency clearly DOES imply disease. DYSFUNCTION is even more clear in articulating that this is not normal and not intentional. For transplant patients, the suppression clearly IS intentional. Do you follow?

My comments were aimed at improving clarity. Instead, since you are dismissing my comments as opinions to be ignored, I think it is not helpful any longer. Sorry to have bothered.
 
R

Robin

Guest
Yeah, I think you are probably (or very probably) right. Klimas didnt actually say anything about the paper being on CFS -- only that it was on XMRV.

It's ambiguous but I think she was referring to XMRV in CFS patients. Look at her slide:

SAcm3.jpg


She went on to discuss the importance of basic science in working out a reliable test, and revealed that she is one of the people providing samples for the test labs.

ETA: I meant to add this to the Klimas lecture thread, but one has been locked and the other deleted.