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New KDM, Lombardi research--HERV

Discussion in 'Latest ME/CFS Research' started by Sushi, Feb 19, 2013.

  1. Valentijn

    Valentijn Activity Level: 3

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    Sort of viruses - an autoimmune reaction to a protein produced by virus fragments which are part of human DNA. But really, the problem is the autoimmunity.

    That said, autoimmune disease can be triggered by proper viruses. So autoimmunity might be the underlying problem, but it could have been a virus that triggered the autoimmunity.

    Then dysregulated immune system possibly results, and abnormal reactions to infections? There's no detailed info about how other symptoms are caused.
  2. alex3619

    alex3619 Senior Member

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    I still haven't read the full paper and I am busy today and will probably be crashed for the next several days, though I am testing something that might get me through it OK. However:

    HERVs are our own genes. They used to be retroviral invaders, but the retroviruses invaded the DNA and became part of us. So this is NOT a viral infection in the normal sense, though there is some speculation that certain viruses might allow HERV genes to become active in combination with new viruses, though I read this stuff a while back.

    The main issue seems to be whether the gene becomes active. If its switched on, it can produce viral proteins, just as the cell can produce beneficial proteins. These proteins might provoke an immune response, and hence might lead to autoimmunity.

    Normal autoimmune processes to eliminate self-responses might not be valid, because these genes are inactive during immune cell (particularly B cell) development, and so cannot provoke a self response. Its only after these genes are woken up, and become active, that the B cells can respond, and autoimmunity might develop.

    Viral infections are suspected of being able to trigger HERV activation. Its not a topic I have looked at a lot recently, so my information is bound to be incomplete and perhaps even wrong. I might need to do some reading on this.

    HERVs are contraversial. If it could be demonstrated that a HERV has resurrected and become infectious that would make waves in medical science. I think some are trying to do that. However it seems to me that dysregulation of HERV genes leading to viral protein synthesis might be enough.

    This may induce local tissue inflammation. We know that most of the latent pathogens suspected in ME, and infecting B cells, become reactivated and infect inflammed tissue. That is the link with existing latent infections.

    HERVs could also affect immune function. This will alter our reponse to new pathogens.

    This research is far from giving conclusive useful results, but its very interesting and perhaps deserves some deep consideration.
  3. Shoesies

    Shoesies Senior Member

    I find this to be of import.

    It is noteworthy that work conducted in
    the laboratory of Dr. Bridget Huber showed that HERV-K18
    expression could be induced by herpes viruses such as
    Epstein-Barr virus and human herpes virus 6 (HHV-6) (34,
    in vivo

    61). Consistent with that work and with the data presented
    here, both of these viruses have been observed in the
    duodenum of individuals with ME (62).
    snowathlete and Valentijn like this.
  4. serg1942

    serg1942 Senior Member

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    Hi guys!

    This is my interpretation of the study:

    http://www.sfc-em-investigacion.com/download/file.php?id=236&mode=view

    Anyone out there willing to help me out with my doubts?

    According to the paper, as far as I understand, the HERV would transcribe some proteins (gag and env) that, as superagents would wreck the normal Antigen Presentation Cell process characteristic of pCD cells, leading to a chronic "improper" activation of lymphocytes T, disruption of cytokines, etc. that in turn would create systemic inflammation, and a humoral response, including complement and antibodies against HERV proteins, that, through molecular mimicry would produce autoimmunity. Then, both the autoimmunity and the alterations of the cytokines, etc., could cause CFS symptoms.

    Ok, everything more or less "undertood" until here. Now my questions, as shown in my sketch:

    - Do the HERV proteins go out of the cell? I know they do, but not sure within this hypothesis...

    - The pDC cell has found to be the only one with immune reactive HERVs proteins, so I assume (I have forgotten to draw this idea in my sketch) that the antiboides against HERV must stick onto the pCD cell membrane, therefore being attacked by lymphocytes, but with little success, as they have being improperly activated because of the HERVS proteins acting as super antigens... This would also deregulate the normal function of this cells... Am I right here?

    - Finally, and more important, what would be the "self target" of this autoimmune process? If HERV proteins go out of the cell, I guess that the target may be any very similar protein (molecular mimicry). By this process, any cell of any tissue could be affected, and this would depend on certain intrinsic characteristics of both the "soldiers" of the immune cells and the potential targets.

    - Any help here to help me out with the interpretation of this all? I'm getting stuck!

    Thanks!
    Sergio
  5. Guido den Broeder

    Guido den Broeder *****

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    Actually, the research seems rather insignificant to me. Most of the paper is speculative. For some time now, KdM has been giving us a brand new cause of ME every year, always completely different from his earlier breakthroughs.

    What is known is that latent herpes viruses can play with our genetic material, which includes HERV. It is conceivable that what genetic material is present affects who can develop ME and who can't, but this article doesn't shed a light on that. I think that ongoing inflammation as such can explain all that has been found here.
  6. serg1942

    serg1942 Senior Member

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    Actually I think this, if confirmed with a bigger number of samples, is an amazing discovery, giving an explanation for the etiopathophisiology of CFS and most autoimmune diseases known as of today... So for me, this COULD be a turning point in many aspects for all of us... Just my impression.

    Sergio
  7. alex3619

    alex3619 Senior Member

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    I still haven't read the paper and my brain is starting to go, and my day is only just starting. I think this is interesting. I also think it could be one more example of pathophysiology and not tell us much about the core illness, as Guido suggests. There have been lots of such Aha! moments, (Eureka! moments) in ME and CFS research. We are slowly mapping out a complex mess of factors, and many of these can cause many of the others. Are there multiple causes? Is there one hidden cause deep inside the mess of pathways? Is it something known or yet to be discovered? Do we need someone with a sharp sword to come along and cut this knot to reveal the true state of affairs? Your guess is as good as mine, or anyone elses. We just are not there yet. (I am facing a long car trip today, so the just not there yet thought seems appropriate.)
    rosie26, svetoslav80 and SOC like this.
  8. Guido den Broeder

    Guido den Broeder *****

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    @Sergio: Really? What exactly does it explain? I am totally accepting that the presence of strange DNA leads to disturbances once molecules come free, but that's the consequence of an inflammatory disease, not the cause, and it doesn't necessarily lead to medical complaints either.
  9. lansbergen

    lansbergen Senior Member

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    What strange DNA? HERV's are endogenous.
  10. Guido den Broeder

    Guido den Broeder *****

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    Even so. It depends on how one sees time, I guess.
  11. lansbergen

    lansbergen Senior Member

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    HERV's are present from the conception.

    Question is what activated them in those patients.

    I can not find herpes does that.
  12. Guido den Broeder

    Guido den Broeder *****

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    I was thinking time as in 150,000 years ago (some HERVs are as recent as that). :)
  13. beaverfury

    beaverfury beaverfury

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    Very grateful for science savvy members sober assessment of research on this forum.
    Otherwise i get too excited over the next big breakthrough and want to go out and buy a crate of poppers.
    snowathlete likes this.
  14. alex3619

    alex3619 Senior Member

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  15. Valentijn

    Valentijn Activity Level: 3

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    Some of it is speculative, but most of it focuses on a specific autoimmune reaction found in ME patients but not healthy controls. The speculative parts are regarding how that autoimmune reaction develops and how it causes symptoms.
    snowathlete likes this.
  16. Guido den Broeder

    Guido den Broeder *****

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    No autoimmune reaction was revealed by this research. The authors hint at autoimmunity many times, but they were very careful not to claim it.

    I see no reason to believe that ME is an autoimmune disease. The organism responds to an actual (entero-)viral invasion.
  17. Valentijn

    Valentijn Activity Level: 3

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    In any case, there's now some very specific starting places to confirm either (autoimmune or retroviral) theory that would explain the immunoreactivity.
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  18. Guido den Broeder

    Guido den Broeder *****

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    The role of pDCs in ME is perhaps the interesting part here but is nothing new. They produce interferon and regulate the immune response to EBV. It seems feasible to me that their activation (which also happens in MS and SLE) can induce a clean-up response.

    I would get curious if the HERVs, rather than the immunoreactivity, were present in ME patients but not in controls.
    Valentijn likes this.
  19. Valentijn

    Valentijn Activity Level: 3

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    Had they been investigated before, especially in an auto-immune context?

    That does seem like something interesting to look for ... but couldn't healthy people have the proteins without the immune reaction to them?
  20. Daffodil

    Daffodil Senior Member

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    someone from the lipkin team told me a while ago, that the disease is looking like an autoimmune one and that what they are finding might help lupus and MS (and other?) patients too....they wouldnt give me details but i think they are on the same wavelength as kdm/lombardi.

    there are already MS and lupus trials going on with antiretroviral agents

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