Lipkin's Microbiome Research -- new or old topic? (split thread)

Daffodil

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by entero, do you mean enteroviruses?

you must read the recent paper about the influenza A activating certain proteins of HERV-W. something has primed us for autoimmune disease and we experienced a further trigger which started this cascade.

enteroviruses are just more co-infections can cannot control.

even EBV Is likely not the cause..it just may have played a part in the trigger.

there will be more details in the next paper.....there is a reason the HERV proteins weaken the immune system...there is a mechanism by which this is going on (don't ask for details because i do not know them).

i was just at a neighbour's house watching the oscars. one of the women there was telling me how a woman who had a home invasion and witnessed her entire family killed, developed full-blown RA right after.
 

vli

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Sorry if I seem too daft here, but what I meant @Daffodil was I was hoping someone could explain THIS to me:
If the HERV is being expressed wouldn't something still have to be causing it to be expressed (be it a virus and/or toxin)?? And shouldn't you then be trying to find out what that virus is (and I'm not saying it's EBV; I'm just using it as an example?)??

So regarding what's causing the HERV expression, Chia has lots of tissue biopsies showing enteros, which is a big deal b/c unlike HERVs, enteros shouldn't be there—they are an outside pathogen, and Chia’s found them in tissue. Shouldn’t that be a smoking gun?
 

Sushi

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@vli said:

If the HERV is being expressed wouldn't something still have to be causing it to be expressed (be it a virus and/or toxin)?? And shouldn't you then be trying to find out what that virus is (and I'm not saying it's EBV; I'm just using it as an example?)??
I believe that is what some of the ongoing research is looking at.

Sushi
 

vli

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I believe that is what some of the ongoing research is looking at.

Sushi
Yes but is it accurate to say that KDM's current research is not so much focused on that, but rather on trying to develop something that will stop that expression?

Or maybe an additional question: is it fair to say that Chia has been trying to find out whether the trigger for any HERV expression is an enterovirus (and this is, in fact currently not KDM's focus)?
 

Sushi

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Yes but is it accurate to say that KDM's current research is not so much focused on that, but rather on trying to develop something that will stop that expression?

Or maybe an additional question: is it fair to say that Chia has been trying to find out whether the trigger for any HERV expression is an enterovirus (and this is, in fact currently not KDM's focus)?[/user]
We actually don't know as this research is unpublished and we have no details. It can't be discussed outside of the circle of the participating researchers without jeopardising publication. All we can surmise is that the questions raised in the published Feb. 2013 research are being further investigated.

Sushi
 

Daffodil

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why does something have to be driving the HERV expression? couldn't it be that it is triggered and now it is just an ongoing process?
 

vli

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why does something have to be driving the HERV expression? couldn't it be that it is triggered and now it is just an ongoing process?
Maybe we're misunderstanding each other a little here. I never said anything had to be currently DRIVING the expression. I was asking in my post prior whether it was known that KDM IS indeed trying to find that trigger, because from what I've seen enteros look like good candidates--because they were found in tissue and they shouldn't be there--unlike HERVs, they're from the outside.

vli
 

MeSci

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Can't remember if this has been discussed before with regard to HERV (I have a feeling it has) but maybe the issue is our old 'friend' molecular mimicry, whereby (theoretically) an antibody to a pathogen - or in this case a former pathogen that has become part of the host - also mistakes one or more of the host's own proteins for those of the pathogen/former pathogen and attacks them, i.e. autoimmunity occurs. A similar process has also been proposed for autoantibodies against heat shock protein 60 (HSP60) in relation to mitochondria, which has also been discussed here and in my blogpost.

Thus just because antibodies raised against HERV reacted with the duodenal samples, it doesn't necessarily indicate the presence of HERV or any part thereof. HERV or parts thereof may have been present at some time but not any longer. The lab-produced antibodies may be reacting to something else.

I suspect that this process has occurred with a wide range of pathogens in the aetiology of ME and other autoimmune diseases. What we need to look for is perhaps not specific pathogens but the underlying situation that allowed autoimmunity to develop, e.g. gut dysbiosis/leaky gut or disruption of the blood-brain barrier (BBB). Gut-based causes are probably much easier to address than BBB-based causes.
 
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Firestormm

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Yes, he published in Feb 13 but is preparing to publish again. In Feb 13, the article said:

(http://iv.iiarjournals.org/content/27/2/177.full)

At that time they had confirmed that antibodies against HERV proteins had been found, but, at that point no specific HERV proteins were identified. The next article will, I'd guess, elucidate their further research.

Sushi
I gather that identifying the exact HERVs is very difficult so thanks @Sushi it’s not surprising that KDM would take a while to do it.


But sorry, I have more questions…


I started reading your posts and trying to understand your views in the first place because I genuinely wanted to understand HOW as @Daffodil says KDM is “ten years ahead”.

we all have HERVs, but we don t know yet whether HERV expression is the cause rather than effect of the main pathology. For instance someone suggested that a virus say EBV may be causing the HERV to be expressed-in which case, the chain of causation (if I've understood correctly) would be: EBV causes HERV expression, which in turn causes ME. If the HERV is being expressed wouldn't something still have to be causing it to be expressed (be it a virus and/or toxin)?? And shouldn't you then be trying to find out what that virus is (and I'm not saying it's EBV; I'm just using it as an example?)??

So regarding what's causing the HERV expression, Chia has lots of tissue biopsies showing enteros, which is a big deal b/c unlike HERVs, enteros shouldn't be there—they are an outside pathogen, and Chia’s found them in tissue. Shouldn’t that be a smoking gun?


I’m trying to be fair, I really am… but the little more that I try to understand of this issue everyday, the more I feel there’s more evidence AT THE PRESENT TIME for enteros to be the cause of ME than there is for HERVs to be. AND just because I say that doesn't mean I'm saying HERVs and enteroviruses are mutually exclusive, (so please don't put words into my mouth--thanks!!), especially if an entero can be proved to be the trigger for the HERV expression. Apart from what I said about the smoking gun of an outside pathogen being found—I feel enteros could be the cause because they've already been shown to be able to cause a LOT of probs like polio and viral myocarditis, and it is veery interesting that post-polio syndrome is so incredibly similar to ME. OTOH, HERVs have yet to be shown to cause a human disease, ALTHOUGH I’m by no means ruling them out (again, I’m just trying to learn here!!!).

Can anyone here illuminate me a bit more??
Thanks for the paper Sushi :) I can't remember if I read it before or not (they all tend to get mushed in my brain until I re-read them :))

In so far as I could tell from a read through, the paper was also saying they had not - and indeed no research had - been able to establish HERV expression as being a cause of disease. It was being looked at in other conditions - I think MS was mentioned as also being consider autoimmune and that HERVs may play a role - but no link had yet been established. But that discussion is really outside of the research conducted in this paper, which would need replicating on a larger scale. Any treatment therefore - also not relevant to this paper - remains speculative at best: assuming any treatment is recommended on the back of said research.

Am I wrong? Thanks. I am generally crap at reading papers - the detail is over the top of my head I am afraid.
 

Daffodil

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didn't lipkin also find some retroviral sequences in our blood but didn't know the significance or if there was any? retroviral sequences are found in many diseases such as ALS or MS. could this be HERV proteins?

lets also remember that antiretrovirals helped several with CFS...I know of one woman who recovered on AZT, another young boy who recovered on Raltegravir, and of course, several (including myself) who were helped by Viread.

sorry, but I don't think the answer is in poop. might not even be in blood.
 

Firestormm

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didn't lipkin also find some retroviral sequences in our blood but didn't know the significance or if there was any? retroviral sequences are found in many diseases such as ALS or MS. could this be HERV proteins?

lets also remember that antiretrovirals helped several with CFS...I know of one woman who recovered on AZT, another young boy who recovered on Raltegravir, and of course, several (including myself) who were helped by Viread.

sorry, but I don't think the answer is in poop. might not even be in blood.
You do realise that individuals 'recovering' because of any given treatment outside of trial (randomised, controlled and possibly even one using a placebo such as a sugar pill/ inert powder/salt water) don't really cut the mustard when it comes to pronouncements of efficacy.

How do you know they wouldn't have 'recovered' anyway? Or that their recovery was part of a cycle and they will relapse in future? Or that they didn't respond to a treatment because of a comorbidity? ME is a disease whose process is unknown and for those who meet the diagnostic criteria (of which there are many) a conditon that is heterogeneous in large part and at the present time.

There's lots of these stories - and I don't doubt what it means for the individual or even for patients who take a treatment (usually a pill or powder) and feel better because of it. Hell, I take symptom management prescriptions myself and think they are doing some good.

But when it comes to treatments that are being said to address the disease itself or to some process said to have direct bearing on the unknown disease process - I have to ask about evidence.

We are so desperately short of proper clinical trials but not short of purported treatments, that the situation makes me weep in frustration: even things like GcMAF need a clinical trial before half of the claims made by e.g. manufacturers, should be made - let alone subsequent (or sponsored) advertisements.

But most patients when seeing a clinician - especially an expert - will try what is recommended especially I would suggest one that hasn't been trialled (what I mean is they will be less inclined to refuse): but unless there is a clinical trial how do you know you aren't reacting to placebo i.e. not the substance (if indeed it has any medicinal benefit in humans) but that whole environment of seeing an expert, paying for his time, being nicely treated, and prescribed something that might help etc.?

I am not saying anyone is - I am saying we need to demonstrate (as much as possible) that we aren't.
 

Sushi

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Thanks for the paper Sushi :) I can't remember if I read it before or not (they all tend to get mushed in my brain until I re-read them :))

In so far as I could tell from a read through, the paper was also saying they had not - and indeed no research had - been able to establish HERV expression as being a cause of disease. It was being looked at in other conditions - I think MS was mentioned as also being consider autoimmune and that HERVs may play a role - but no link had yet been established. But that discussion is really outside of the research conducted in this paper, which would need replicating on a larger scale. Any treatment therefore - also not relevant to this paper - remains speculative at best: assuming any treatment is recommended on the back of said research.

Am I wrong? Thanks. I am generally crap at reading papers - the detail is over the top of my head I am afraid.
Nope they didn't say that HERV expression was the cause of any disease--only that they found it, and we can surmise that they are trying to look into it further. This research has not led to any treatment recommendations that I am aware of.

Hopefully, one day....

Sushi
 

vli

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I am not sure the trigger is that important
I disagree. IF enteros ARE the trigger for the HERV expression, wouldn't you want to turn them off??! I understand that the goal is to develop a drug that will stop the HERV expression but I am not sure it is so easy to turn off HERVs all over the body.

Maybe there are two points of attack here: you can develop a drug to stop the HERV from being expressed, or a drug that stops the thing that's triggering the expression in the first place (the actual cause of the pathology).
 

serg1942

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Hi guys, hi Vli,

When it was published I read the paper thoroughly and made an in deep summary of it in Spanish:
http://www.sfc-em-investigacion.com/download/file.php?id=238

Please, take a look at the draft of the first page. It describes in a very simple way what the paper found, the theoretical autoimmune pathway that could lead to CFS and the questions left unanswered:

http://www.sfc-em-investigacion.com/download/file.php?id=238

VLI: There's a known autoimmune process, called autoimmune mimicry, that perfectly fits with what this paper found. What this paper found are HERVs' proteins, but not a particular HERV.

- Lets make clear that HERV's expressing proteins acting such a superantigens should not be there.

- Some pathogens have shown to be able directly or indirectly to trigger this autoimmune cycle, including: EBV, HHV6, or even Borrelia (by attaching to the TCR receptor). So under this view, enteroviruses should be seen as another possible trigger.

- Why to try to replicate this study instead of go with the microbiome study? Because, as some fellow pointed out, the problem with CFS studies is always the same: a low "n" (number of patients/controls) and no proper (if any) replication studies. If the "n" here would have been 100 instead of 12, this would have reached a much more higher level of repercussion.

- Remember XMRV? I was found positive by two different labs, both in blood and by biopsy (PCRs). I don't mind about the name of the sequence they found. But a fact is that they were finding antirretroviral proteins. If not exogenous as thought, then it must be endogenous: HERVs.

- There's no way to know if KDM-Lombardy-WPI are looking for a specific HERV, or rather for a way to break this autoimmune vicious cycle. In any way, it seems to me the way to go. I think most abnormalities known in CFS could be tracked down to this cycle. I do think it's worth following this lead.

- I believe remember reading that Lypkin was trying to find a virus hidden inside WBCs in the gut. Well, KDM et al found specific macrophages of the gut expressing HERVs proteins only in CFS patients. Again, it fits.

- LYME! Come on... it's probably one of the main triggers. Actually it is officially known to cause, as an acute infection, an autoimmune mimicry vicious cycle as a mechanism of infection....

- Why some people develop multiple sclerosis and others CFS? well, again, as another fellow stated: genetics, epigenetics... Also probably different HERVs. Again, KDM paper didn't find an specific HERV, but HERV proteins.


-RITUXIMAB: Remember it helped and even cured some PWCFS (same problem, low "n"): take a look at my diagram: if you kill the B cells, you break the cycle... So, again it fits...

- And finally, someone said there wasn't enough proof for stating they had found HERVs proteins. Actually if you read the paper, they used 3 different methods to assure this (See at the end of my post).

Hope it helps,

Sergio


(...)eight samples of the duodenum were immunoreactive to antibodies raised against HERV proteins(...)Additional analysis was conducted using two anti-gammaretroviral antibodies (...)The observed immunoreactivity was reproducibly consistent with the previous anti-HERV results, suggesting that the antigammaretroviralantibodies were cross-reactive with the HERV antigen (...) Our detection of proteins that react with monoclonal antibodies to HERVs is consistent with HERV expression. Nevertheless, it could be argued that an exogenous retroviral infection may potentially account for the observed results (...)cryopreserved lymphocytes and preserved RNA from a duodenal biopsy were available from two HERV-positive ME cases. Therefore, we performed unbiased next-generation sequencing (NGS) on both RNA derived from the duodenum and purified pDCs from these individuals. Multiple contigs of known HERV genes were observed; however, no open reading frames were identified that could account for an infectious retrovirus (unpublished data) (...)
 

Daffodil

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Hi guys, hi Vli,

When it was published I read the paper thoroughly and made an in deep summary of it in Spanish:
http://www.sfc-em-investigacion.com/download/file.php?id=238

Please, take a look at the draft of the first page. It describes in a very simple way what the paper found, the theoretical autoimmune pathway that could lead to CFS and the questions left unanswered:

http://www.sfc-em-investigacion.com/download/file.php?id=238

VLI: There's a known autoimmune process, called autoimmune mimicry, that perfectly fits with what this paper found. What this paper found are HERVs' proteins, but not a particular HERV.

- Lets make clear that HERV's expressing proteins acting such a superantigens should not be there.

- Some pathogens have shown to be able directly or indirectly to trigger this autoimmune cycle, including: EBV, HHV6, or even Borrelia (by attaching to the TCR receptor). So under this view, enteroviruses should be seen as another possible trigger.

- Why to try to replicate this study instead of go with the microbiome study? Because, as some fellow pointed out, the problem with CFS studies is always the same: a low "n" (number of patients/controls) and no proper (if any) replication studies. If the "n" here would have been 100 instead of 12, this would have reached a much more higher level of repercussion.

- Remember XMRV? I was found positive by two different labs, both in blood and by biopsy (PCRs). I don't mind about the name of the sequence they found. But a fact is that they were finding antirretroviral proteins. If not exogenous as thought, then it must be endogenous: HERVs.

- There's no way to know if KDM-Lombardy-WPI are looking for a specific HERV, or rather for a way to break this autoimmune vicious cycle. In any way, it seems to me the way to go. I think most abnormalities known in CFS could be tracked down to this cycle. I do think it's worth following this lead.

- I believe remember reading that Lypkin was trying to find a virus hidden inside WBCs in the gut. Well, KDM et al found specific macrophages of the gut expressing HERVs proteins only in CFS patients. Again, it fits.

- LYME! Come on... it's probably one of the main triggers. Actually it is officially known to cause, as an acute infection, an autoimmune mimicry vicious cycle as a mechanism of infection....

- Why some people develop multiple sclerosis and others CFS? well, again, as another fellow stated: genetics, epigenetics... Also probably different HERVs. Again, KDM paper didn't find an specific HERV, but HERV proteins.


-RITUXIMAB: Remember it helped and even cured some PWCFS (same problem, low "n"): take a look at my diagram: if you kill the B cells, you break the cycle... So, again it fits...

- And finally, someone said there wasn't enough proof for stating they had found HERVs proteins. Actually if you read the paper, they used 3 different methods to assure this (See at the end of my post).

Hope it helps,

Sergio


(...)eight samples of the duodenum were immunoreactive to antibodies raised against HERV proteins(...)Additional analysis was conducted using two anti-gammaretroviral antibodies (...)The observed immunoreactivity was reproducibly consistent with the previous anti-HERV results, suggesting that the antigammaretroviralantibodies were cross-reactive with the HERV antigen (...) Our detection of proteins that react with monoclonal antibodies to HERVs is consistent with HERV expression. Nevertheless, it could be argued that an exogenous retroviral infection may potentially account for the observed results (...)cryopreserved lymphocytes and preserved RNA from a duodenal biopsy were available from two HERV-positive ME cases. Therefore, we performed unbiased next-generation sequencing (NGS) on both RNA derived from the duodenum and purified pDCs from these individuals. Multiple contigs of known HERV genes were observed; however, no open reading frames were identified that could account for an infectious retrovirus (unpublished data) (...)
Sergio...this is exactly what I am saying! I asked the Lipkin camp long ago about trying to replicate the KDM study but received no response.

When KDM says 'CFS is Lyme', he probably means that it is the same autoimmune process involved in both diseases; both diseases have low NK cell function and a weakened immune system. When chronic lyme patients stop their antibiotics, they get sick again.

I met a 'CFS/ME' patient who had been functioning close to normal for 11 years, working full-time...but she had been taking antibiotics for the entire time! There is something else going on other than just pathogens here, and we need to support those who are looking into this, in my opinion.
 

Daffodil

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ok I know I said I wasn't objective....and maybe I am not....and I know I am sounding like a broken record. ..but I really feel that the microbiome study is going lead us along another dark hallway.

the recent paper which showed how influenza A can activate HERV-W gag proteins...these are the types of papers we should be supporting if we want real treatment. there has been communication between this team and the WPI.

SUPPORT WPI
 

serg1942

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Hi Daffodil.

I totally agree with you... As far as I understand, KDM sees that most PWCFS have Lyme, and that Lyme, interacting with the TCR receptor (and probably by other indirect routes), contributes to this negative vicious cycle, that IS NOT NEW. The new thing here is to have found that ONLY the macrophages of the gut, known as plasmacitoid dendritics cells, are the ones expressing HERV proteins, and ONLY in PWCFS and not in ANY healthy control... This is important to highlight! We have a specific cell to look at, in the gut!!! This is big, and it is a fact. The flaw is the low number of participants in the study...that's why we need another study to confirm it!, then the pharmaindustria will have a very very sweet candy to put money in... But only if another team, and if possible with higher "n", replicates the results.




BTW, could you please give me the link of this study about influenza??




Thank you!


Sergio