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ME/CFS: A disease at war with itself
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Dr. Jay Levy found no XMRV in my blood

Discussion in 'XMRV Testing, Treatment and Transmission' started by mojoey, Nov 22, 2010.

  1. mojoey

    mojoey Senior Member

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    Hey Alex,

    If Cort's case pans out as the trend rather than the exception, that would imply that the higher-functioning individuals have more antibodies.

    I don't think the history of this disease has shown things to be as simple as you describe. What seems more likely is that we have excess inflammation along with immune deficiencies. NK cells are low, whereas certain cytokines are high. The CD4/CD8 ratio is the mirror of AIDS. Neutrophils are in the basement, and Rnase-L enzyme activity is through the roof.
     
  2. alex3619

    alex3619 Senior Member

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    Hi free at last,

    Antibodies derive from B cells. These cells have their own cytokine profile but its been a decade since I looked at this and science has probably evolved a lot in this area. However there are other elements of the immune system - it is hard to say which parts of the immune system are producing which cytokines to produce which symptoms. We are still guessing. I think much of the illness is our own immune profile, but the trigger would be one or more of:

    1. viral load (so more antibodies mean less symptoms)
    2. viral envelope (we can have antibodies to that, it may be the most likely target, and this could reduce symptoms)
    3. cell signalling (infected or quasi-infected cells signalling distress). This is the most complicated option. In theory many of these cells would self-destruct or be destroyed, so their number would decrease over time. With lower viral load due to antibodies etc., we could expect fewer cells to be infected. However, this is very complicated and I know too little about immunology to give a good guess on something so arcane. If this option is correct, it may take many years of research to discover what is happening.

    Of course there could also be other triggers I am not thinking of at the moment...

    bye
    Alex
     
  3. free at last

    free at last Senior Member

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    Ok cheers for that Mojoey

    I should probably stay out of this by the looks. But if immunity is not ramped up as you say when sick. surely higher functioning individuals would be showing lower antibodys ? lost on that a little. Im not talking about inflamation as preventing function ( though i agree i should be ) as it also prevents function. But more the sickness aspect that arises from a immune response. Not the whole picture have i asked agreed. so i assume inflamation is producing cytokins producing symptoms ? just edited out of my depth here.

    . Surely the sickness aspect would still show higher antibodys ? I guess your saying no. I was at my worst functioning, when i had the highest immune response with the temperatures ? Ok back to college for me then.
     
  4. alex3619

    alex3619 Senior Member

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    Hi mojoey, in one case I would agree that it would show that higher functioning individuals have more antibodies. Those individuals would have to be in partial remission. Higher functioning individuals who are not in remission but haven't become really sick yet might simply have a low viral load. This hypothesis is testable, so I hope somebody at least looks at it once we can accurately measure viral load.

    I don't think it is simple as an inverse correlation between adaptive and innate immunity. The Rnase L problem is an innate response, and it is highly ramped, but the NK cell function is innate but very suppressed. Its complicated. I think its more that some parts of the immune system are suppressed, so other aspects of the immune system ramp up and compensate. Which these are could vary between individuals.

    There is one other issue too. If the immune system loses track of the virus and thinks its gone away, it will quiet down and so will our symptoms. This doesn't necessarily mean the virus is under control. It may mean we have lost the fight and the virus is out of control. This kind of patient would be largely symptom free for years or decades, but their cancer risk would steadily climb (presuming that X actually causes cancer).

    Bye
    Alex
     
  5. free at last

    free at last Senior Member

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    Just read your Post Alex, so i guess your saying antibodys do not create symptoms. So is that true indirectly ? in other words they do not turn on cytokine production ? i may to a degree fit the symptomless xmrv + type you speak of. though not intirely. as symptoms do re occur. but seem to be getting less the longer this goes on. cancer is a worry here isnt it ?
     
  6. alex3619

    alex3619 Senior Member

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    Hi free at last, cancer is a worry for everyone with XMRV unless it can be proved it doesn't cause cancer. Antiretroviral therapy, or even better therapies that we have yet to develop, can't come soon enough. bye Alex
     
  7. mojoey

    mojoey Senior Member

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    Very true. Thanks for correcting me on the Rnase-L
     
  8. mojoey

    mojoey Senior Member

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    I don't know if this is true. The oncogenesis happens on a pro-viral level right? And it seems like it's mainly Immunity in the form of apobec3 enzymes and other internal enzymes that hypermutate the coding of retroviruses to prevent the expression of oncogenes. I think antibodies that are being tested for thus far lock onto actual unintegrated virus which are not (yet) the direct cause of oncogenesis. Of course, antibodies that latch onto surface antigens expressed by cells that have been infected by the virus would fit into your theory. Antibodies in this case would be targeting whole infected cells that harbor oncogenes.
     
  9. alex3619

    alex3619 Senior Member

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    Hi mojoey, You could be right - and I suspect that the primary target for antibodies by the immune system is the envelope. We just don't know. I really wish some time traveller from 2110 would send us a copy of a textbook on all this.

    Unintegrated virus in the blood I expect to see rapidly destroyed, and is probably of little consequence except as a marker. I also think we may find the virus likes to pump out pure envelope as a toxin, but I have yet to see evidence of this.

    If antibodies are targeting infected cells, it is probably the RNA that is triggering it. Viral RNA tends to set off cellular alarms.

    I suspect (my current impression with current data) that APOBEC3 is a big part of why we don't get full blown AIDS and die. It will also slow the spread and expression of the virus. However, some cell lines don't have APOBEC3 and some researchers already think that this is why the virus can cause prostate cancer. I am willing to entertain the notion that the cancers we find XMRV in are in those tissues for which either APOBEC3 is not expressed, or some other factor has limited or stopped APOBEC3 activity.

    Please also keep in mind that cleaved RNAse L is extremely antiviral, and is another big part of our defense, although it seems that most researchers are not really looking at it for the moment. I would really like to know the tissue distribution of the increased RNAse L activity, but I am unaware of good recent research on this.

    The other problem is this: once the viral DNA is inside the nucleus or integrated with our DNA, most of the defenses will be limited, perhaps severely or completely, I am unsure about this at the moment. These are the cells that might develop cancer. The body can fight the viral RNA (and viral proteins) that are produced after this, but it has to keep doing so. Like with most cancers, the cell probably successfully defends itself millions of times. It just takes one failure to give rise to a cancerous cell, and after that it is up to the immune system to detect and destroy it before it grows. There is so much that we don't know about this ... where is that time traveller?

    Bye
    Alex
     
  10. FunkOdyssey

    FunkOdyssey Senior Member

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    I am also non-flu onset, pretty functional, culture negative and XMRV antibody positive via VIPdx, very interesting. Also have low WBC (3-3.5) mostly neutrophils that are lowest and dragging it down, low platelets (100-130), and low CD57 NK count (36).
     
  11. Hi MoJoey,

    Does this mean that they did find the virus by serology - just not culture/PCR?

    I have a theory, and it just my own research, that those with sustantial Vit D status or high blood D analogues (which act like ARVs) - may clear their blood more efficiently of X/MRVs. I had a fever for years that I couldnt get rid of until I took high levels of D daily. If I step off the Vitamin D pedal for even a short time - my fever comes back.

    I spent a great deal of time trying to reverse engineer the value of Vit D for me - especially it's AVR-like peptides.

    So I wonder if those with long-standing illness that can clear their blood through whatever mechanism - have a negative culture/PCR and positive serology?

    Something is at work here for the disparate results on testing mild VS severe cases - and having one positive and one negative.

    Just throwing this out here - the whole culture/PCR vs Serology phenomena...and my theory.

    Elisabeth
     
  12. mojoey

    mojoey Senior Member

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    Hey Elisabeth,

    I still have not gotten an answer as to what type of test Dr. Levy did. I will ask again. So far I am positive by VIPdx culture, but haven't gotten my serology results yet
     

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