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A Little Poisoning Along the Road to ME/CFS
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Molecular Mimicry, Autoantibodies, HGRVs, and Rituximab

Discussion in 'XMRV Research and Replication Studies' started by beike, Oct 31, 2011.

  1. beike

    beike

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    Proteins of the XMRV retrovirus implicated in chronic fatigue syndrome and prostate cancer are homologous to human proteins relevant to both diseases.

    http://precedings.nature.com/documents/4669/version/1

    Anyone remember this paper? If the HGRV present in people with CFS is similar to the sequence used in this paper, could the reduction in CFS symptoms in the recent Rituximab trial be due to reduction of infected B cells? Or could it be that the b cells population that produces autoantibodies to the proteins mentioned in this paper are depleted and thereby reduce symptoms? Better said, could this be a retrovirally induced autoimmune disease?
     
  2. anciendaze

    anciendaze Senior Member

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    Viral infection is the primary cause of changing B-cell epitopes from CD19 to CD20. The usual explanation is that this is due to EBV, which is practically endemic in humans. The persistence of autoimmune response is something of a theoretical problem.

    Part of the answer could come from EBV, a member of the herpes family which inserts its own DNA through pores in the nuclear membrane. Persistent active infection could generate antibodies aimed at something inside that membrane. A retrovirus could also result in antinuclear antibodies, because with its RNA transcribed to DNA and integrated into chromosomes, active infection would also provoke immune attacks on the cellular machinery generating the offending proteins.

    Several members of the herpes family of viruses have been partially implicated in this disease: HSV-1, HSV-2, EBV, VZV, HHV-6. HHV-6 is even found integrated into chromosomes, which herpes viruses are not supposed to be able to do. We even have examples of cell lines derived from prostate cancer "constitutively producing" both a gamma retrovirus (JHK) and EBV.

    Our problem comes from virologists who started classifying this as contamination 40 years ago, and have never seen fit to question their own views. Even when one such virus comes from humans, as above, they insist the retrovirus must have come from a mouse -- because there are no known human gamma retroviruses. A review of the literature convinced me that type C virions have a marked tendency to appear in cell lines associated with particular classes of cancers, like lymphomas or adenocarcinomas. Beyond simply indicating that the etiology of the cancer was unknown, (thus a likely subject of research,) the appearance of such a C-type retrovirus, and dismissal as a contaminant, seems to be a good predictor of poor future progress on etiology.

    I believe we are seeing dual infection by herpes viruses, or possibly others, and a small retrovirus. With typical viral genomes in the herpes family running around 170,000 base pairs, and the suspect retroviruses around 8,100 base pairs, it would be no trick at all to slip the entire retrovirus inside a herpes virus. The retrovirus could be parasitizing a virus which human immune systems tolerate. The exact relationship between the two needs to be elucidated.

    As always, these are personal views without the weight of authority.
     
  3. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    These herpes viruses arent suppose to replicate in normally healthy people, they commonly reactivate in HIV and cancer patients on chemo or organ transplant patients on immuno suppressants, supposedly. So why do many cfs patients have these viruses reactivate have t-cell sub set dysfunction and nk dysfunction. I dont know how this is ignored by the authorities, if its not some type of immune deficiency then some other underlying infection causing immune suppression seems valid, you wonder why that havent looked deeper into this. Even improvement made by patients on antivirals doesnt seem to ring any bells for most docs, what the?? Its been staring them in the face for years but the choose to ignore it, luckily there are some docs out there helping us, we just need it to be common knowledge and not ignored.

    cheers!!!
     
  4. alex3619

    alex3619 Senior Member

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    Bacterial Cardiolipin Hypothesis

    Hi, I would like to propose an additional hypothesis. This is not limited to XMRV or MLLVs, but it would fit here too. THIS IS ONLY SPECULATION AT THIS POINT - its a model not reality.

    Presume that XMRV or a similar murine leukemia like virus invades the infects the resident gut immune cells. Gut immunity declines. (There are other patterns, other details than this, this is just a tentative first step in this hypothesis.) Gut wall integrity declines because of a enterovirus or similar insult. Gut bacterial breakdown products cross the gut wall and enter the blood. The liver is stressed, glutathione has been depleted. The bacterial products should have been cleared by the liver but now make it to the general bloodstream. The immune system reacts. The first half of this story we know, LPS induces a cytokine reaction, eventually resulting in a permanent cytokine shift - this might or might not be the cause of the Th2 bias often found. The research by Maes points toward this, and KDM has done some important work on this also, showing that severity of illness is correlated with LPS levels.

    The second half of the story is interesting. We have been presuming that the anticardiolipin antibodies found in nearly all CFS and ME patients is due to mitochondrial reaction. This might not be so.

    Escherichia coli manufactures its own cardiolipins. Cardiolipin is really a family of chemicals, a phospholipid. If it crosses into the blood stream it can be targeted by the immune response.

    So the etiology of the anticardiolipin antibody is not mitochondria in this model, its bacterial breakdown products translocating to the immune system due to poor gut immunity and integrity. I do not currently ascribe to the view that whole bacterial are crossing over in any numbers - this would probably induce toxic shock.

    But wait, thats not all! Once anticardiolipin autoantibodies are made, they can then attack the mitochondria. So now we have an immune storm and energy depletion. This is a popular hypothesis but I wonder if its not a weak link. It is possible this does not actually happen as the antibodies can't reach the mitochondria. In this case the anticardiolipin antibodies are just a clue, not pathological.

    The brain is the most vulnerable organ to mitochondrial damage. Nerves have a critical reliance on functional mitochondria, which is why mitochondrial disorders frequently show up as neurological disorders first, typicall deafness. So cytokines and mitochondrial dysfunction combine to induce neurological dysfunction. This in turn can lead to autonomic symptoms including orthostatic intolerance. So now we have an immune storm, energy depletion and autonomic symptoms. The order of this is important I think.

    Why was I thinking along these lines? Dr Speedy's site recently brought attention back to an old study that showed nearly all of us have anticardiolipin antibodies. These can attack the mitochondria. Mitochondria are evolutionarily specialized bacteria. So we have antibacterial antibodies with autoimmune overlap. This is about homologous phospholipids, not homologous proteins, but viral assault on the gut immune system could well be the trigger. (The reason Dr Speedy's site mentions this is it this research predicted Rituximab would work.)

    This also fits with entervirus and herpes virus models. If gut immunity is not restored, the problem never goes away.

    After kicking this around for a bit I might write it up as a blog.

    Bye
    Alex
     
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Also do we think that the metabolism is down regulated by the hypothalamus by increasing reverse T3, lowering cortisol production etc and this reducing of metabolism is the bodies protective mechanisms for reducing damage to mitochondria as there is now less demand on them, but less cortisol increase inflammation etc??? I suppose its a horse or the cart thing but thyroid/cortisol can have a role in many symptoms like orthostatic intolerance, immune dysfunction etc.

    The retrovirus that your saying starts the domino effect, would be best to treat and everything would follow/reverse or do u think that the dysfunctions found along the way are going to need to be treated or even just being able to control the cytokine storm could bring about good improvement. I often wonder if the people that improve with hydrocortisone are getting improvement from its anti-inflammatory effect on cytokines too.

    Could the autoimmune side of things be occurring as these retroviruses or herpes virus are now intergrated into our cells and our immune system is trying to fight these infections and in doing so attacking itself?? And these little buggers are in our B-cells??

    There seems to be alot of dysfunctions going on that can effect each other and turn into a viscious cycle, do we try to interrupt the cycle or treat all the dysfunctions one at a time and see if good things follow. Im getting dizzy thinking about it, theres so many interlocking things going on.

    cheers!!!
     
  6. anciendaze

    anciendaze Senior Member

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    There are many, many signs that something is wrong. The problem is fitting the essential ones into a working model that inspires useful questions. You will always end up ignoring some until later.

    Alex3619 has made a good point about enteric bacteria. This need not be entirely at odds with other hypotheses. Provoking a massive response to bacteria in the gut might be exactly the thing which would benefit a retrovirus infecting immune cells. Clonal expansion of responding cells would increase numbers of copied provirus without the virus needing to generate virions. This kind of feedback loop between pathogens and their host environment is not at all surprising.

    The gut also plays a role in infection. We now have a model of viral camouflage using fragments from gut biota in the case of MMTV. This allows the virus to cross over to cells in the wall of the digestive tract without being recognized as hostile.
     
  7. alex3619

    alex3619 Senior Member

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    Hi Heapsreal, I am going to be looking at this too, it seems a real possibility. Bye, Alex
     
  8. bel canto

    bel canto Senior Member

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  9. Enid

    Enid Senior Member

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    Thanks to you all for this interesting informed discussion ..... never doubted in my 12 years viral cause whatever follows.
     
  10. currer

    currer Senior Member

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    http://www.mecfsforums.com/index.php/topic,3241.0.html
    http://en.wikipedia.org/wiki/Cardiolipin

    I couldnt help but note the reference to parkinsons disease. Also the cross reactivity between HIV proteins and cardiolipin.

    I think we could learn much from continuing Mikovits work in looking at disease patterns in families.
    To say ME is an autoimmune disease does not go far enough, as an underlying infection could manifest in different ways, as ME primarily in women, who would be more likely to develop an auto immune state, and parkinsons or cancer etc. in men.
     
  11. SilverbladeTE

    SilverbladeTE Senior Member

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    Somewhere near Glasgow, Scotland
    also, we need to remember, that if it is a specific infectious agent that causes ME...it may present different effects in different types of people!

    IE
    Women may develop ME more often, and men may suffer something else as a more common effect..who knows..perhaps cancers or Chron's Disease or whatever
    but since no one has been LOOKING for such, it may have been entirely missed.
    as the Medical world is still largley dealing with treatment than cure, many problems true cause are sitll unknown (like Multiple Sclerosis and Diabetes, we know the effects, not the trigger and until we find the trigger fidning a cure is vastly much more difficult)
     
  12. beike

    beike

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    Interesting ideas everyone. Just a question I had since many people here seem to now a lot about these subjects. Would an autoimmune response to a particular human protein in the body be difficult to detect? Could patients with CFS/HGRVs be screened for autoantibodies to the proteins mentioned in this paper I posted? How difficult would it be to develop such a screening?

    Thanks

    Beike
     

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