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Lipkin finds biomarkers not bugs

Discussion in 'Phoenix Rising Articles' started by Firestormm, Sep 12, 2013.

  1. Legendrew

    Legendrew Content team

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    A few good points here: NK cells however play a more major role in innate immunity - the job of clearing up viruses is generally down to the adaptive immune system with T-cells and B-cells + the antibodies the B-cells produce.

    To me it seems a little strange that despite these results people still hold strongly onto the viral causation. I understand the argument of tissue-specific viruses but I would expect some clues to still be present in these samples. There has to come a point where we come to accept that viruses aren't the major cause of pathology in ME and I think we're fast approaching that - certainly it is worth testing these things to the fullest of our abilities but if the evidence isn't there you have to move on to other hypotheses. I think there is little argument that they are the most common triggering factor, likely due to the immune response they initiate, but if results searching for them keep turning up a blank we need to explore other areas and I think autoimmunity is both the most associated with the viral ideas and also probably the most exciting area at the minute.
     
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  2. Snow Leopard

    Snow Leopard Senior Member

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    The failure to replicate virus results is not a recent phenomena, it is a consistent one over 20 years. Viruses seem to be key triggers for onset of symptoms, but evidence for chronic infection has remained elusive for a long time, and there are many other good hypotheses out there...
     
  3. globalpilot

    globalpilot Senior Member

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    The reason I think viruses may still be involved (not necessarily causal, but involved) is because Dr Chia found enterovirus in about 2/3 of my stomach biopsy cells. Unless the sample was contaminated I just can't see how this cannot be significant. I hope to hear from Dr Chia on these issue - ie lack of enteroviral RNA in the plasma and CSF.

    I do agree, however, it is puzzling there is no RNA of these viruses in the blood if they are involved.
     
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  4. Firestormm

    Firestormm Guest

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    I admit to knowing very little about enteroviruses. I do know that it's possible these widespread infections are not always the cause of disease. I would though like to hear from Dr Chia with regard to Lipkin's work here. Maybe once it's published he will be willing to review? I am sure many doctors involved in ME work will be reviewing the data and hopefully talking to their patients - even if only to reassure.
     
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Definitely should be sub typing. I think many hold onto the virus theory as there is a group of cfsers who improve on antivirals. Myself dont believe it is the cause but treating them can help alot. Nk cells are there for a reason and work with other t cells and b cells. No reason why this dysfunction can reduce e the immune systems ability to contrl viral infections.
    The autoimmune theory so far hasn't had alot of success at all that has been posted by people here?

    Some recent studies show not only nk but cd8 t cells have low function. I believe its these abnormalities that allow one to get a variety of infections or maybe hit and run. I dont know what they would call this, an immune deficiency or dysfunction.
     
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  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Proper accurate testing as well as well defined cfs study participants could account for there inability to find viruses. Doesn't seem to be a problem for lerner Peterson klimas, as well as being able to treat and improve many of them.
     
    August59 likes this.
  7. lansbergen

    lansbergen Senior Member

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    I refuse to believe the immunesystem attacks self for no reason. I always have and likely always will.
     
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  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I dont think lipkins current work has alot to offer. All it seems to be doing is giving us more questions then answers. We will have to wait until its finished.
    Montoya is doing a separate pathogen study?? Do we know when this will be finished??
     
    August59 likes this.
  9. globalpilot

    globalpilot Senior Member

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    Same here. It makes no sense whatsoever.
     
  10. Legendrew

    Legendrew Content team

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    It's an incredibly complex topic and one I plan to explore more in a possible article in the future. Suffice it to say that there is generally a trigger in autoimmune diseases which moves it from a silent (ie non symptomatic) state into a seemingly active and debilitating state. These triggers can include non-self things such as viruses or bacterial infections - but the immune response then appears to be self perpetuating.
     
  11. alex3619

    alex3619 Senior Member

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    Serpins are a superfamily of proteins, and their function is critically reliant on proper folding. We already know we have increased protein misfolding (KDM finding?) and that we have a mechanism for decreased folding: glutathione deficiency. So are septins, while abundant in quantity, really abundant functionally or deficient? I don't know.

    http://www.ncbi.nlm.nih.gov/pubmed/21781239

    Here is a recent review on serpins:

    http://genomebiology.com/2006/7/5/216

    Serpins are involved in regulating proteases, but also as transport molecules, involving both corticosteroids and thyroid hormone. Its worth noting that one of these, corticosteroid binding hormone, may be involved in producing CFS-like symptoms.

    Have a gander at this table: http://genomebiology.com/2006/7/5/216/table/T1

    In order to make sense of Lipkin's finding we need to know which serpins are involved. Until then the range of possible impact is very open to wild speculation.
     
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  12. alex3619

    alex3619 Senior Member

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    If the biospy included staining of cells to be viewed under a microscope, the possibility of contamination is unlikely. If its just an assay to detect presence of the cells, then contamination is possible. I don't recall exactly, but haven't both been done and the biopsies found to be positive?
     
  13. alex3619

    alex3619 Senior Member

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    One theory of autoimmune is due to how the antibody immune system works. The B cells randomly reshuffle some of their DNA to make antibodies ... which have random targets. Any that match native proteins near where this occurs should be eliminated. A few years back there was a paper showing that proteins that are only expressed far from where the B cells are adapting may not lead to elimination of these B cells.

    When the immune cells are activated by something its due to a protein or protein complex match. If there is sufficient activation then the activated cells multiply - clonal expansion. This is when we develop resistance to pathogens - we have sufficient antibodies to fight them. This is what Rituximab targets - it kills B cells. This is what Lipkin found in the earlier paper. Our immune systems are reacting to something.

    B cells might also create autoantibodies in numbers due to cross-reactivity. The cells are responding to something else, but the antibodies have sufficient affinity to self-proteins that they get weakly attacked.
     
  14. Gijs

    Gijs Senior Member

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    (neuro)toxines -produced by microflora- can trigger the immunesystem. I think this is the next step to investigate.
     
  15. Legendrew

    Legendrew Content team

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    Yep - I think it is also worth mentioning that a small degree of autoimmunity with regards to the production of autoantibodies is a good thing. The argument that autoimmunity needs an external stimulus is a little silly when you consider the benefits that autoimmunity has with regard to detecting and successfully fighting cancerous cells. If autoimmunity was a bad things then it would likely no longer exist in the human (and other organisms) population as the genes and traits responsible for it would have not been selected for during evolution.
    Autoimmunity only becomes a bad thing when the immune response gets stuck in cycles over-expressing randomly created autoantibodies and the response that ensues therein.
     
  16. alex3619

    alex3619 Senior Member

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    http://www.jimmunol.org/content/174/6/3137.full

    This is an old paper, so take what it says too seriously. I am citing it to introduce a point. In obesity research high leptin from fat cells is thought to not make it to the brain at a high enough rate, and so does not send proper signals to the hypothalamus.

    Leptin sends a signal to the brain that there is plenty of energy available, crank up the metabolic rate. What if there isn't, if the leptin is derived some other way? If you have low energy capacity.with high leptin, what happens? What happens if the signal is distorted, as found in obesity, and the hypothalamus is not getting the message that there is too much energy?

    Its also worth noting that women make more leptin than men. Is this related to why more women get ME than men?
     
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  17. Marco

    Marco Old blackguard

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    I quite like the theory of the immune system as a cognitive network that arises out of the Santiago theory of cognition.

    No need to discriminate between self and non-self or to consider autoimmunity as necessarily a problem except in the (relatively) rare case of a massive infection.

    In this theory the role of the immune network is not to seek out and kill but to regulate both
    self and non-self within the parameters necessary to maintain the organism's physiological integrity. Therefore a certain level of foreign organisms is tolerated and regulated. Otherwise how could we tolerate our own beneficial bacteria and how would symbiosis (eg mitochondria) have evolved.

    http://combusem.com/CAPRA4.HTM

    Quite possibly bollocks though ;)
     
  18. alex3619

    alex3619 Senior Member

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    Marco Maturana's theory is complicated and requires careful reading and analysis. I met Humberto Maturana, the founder of much of modern systems biology, as I went to one of his two day seminars. Systems that survive are ones that maintain balance, but that does not mean its seeking balance. Its just mechanisms that tend to maintain balance. Systems that adapt or evolve to maintain balance better have an evolutionary advantage.

    Systems view always have to take details into account, and environment, and mechanism and ... Its one reason why so many try to avoid them. Its not easy taking a systems view, nor even easy to know where to put the boundaries for the system analysis.

    What it does imply is that the current state of the system is also a reflection of how it has changed during its history. In other words, its something dynamic. The immune system is definitely dynamic. I would like to see more work on treating the immune system as a dynamic system over time, but alas that is not where the science is going. The research is usually heavily reductionistic, which is what makes it more amenable to scientific enquiry.
     
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  19. Marco

    Marco Old blackguard

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    Hi Alex

    Must have been an interesting seminar.

    I feel there's a lot in the theory but as you know its getting on a bit now - I don't know if mainstream medicine has embraced any of it - plus while these theories have been highly influential (and influenced by) cybernetics and chaos theory - Varela and Maturana may have over-extended the theory into areas where they've less expertise.

    I do like the idea though that autoimmunity may involve a failure of connectivity in the immune network (Broderick I believe suggested something with regard to immune findings in ME/CFS).

    There's also the possibility that complex systems (as the immune system must be) may be prone to rapid flips to another stable (but dysregulated) state.

    All intellectually satisfying but unlikely to be of any practical help in the near future.
     
  20. snowathlete

    snowathlete

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    It does seem like some pathogens favour tissue but many, including Borrelia, are often enough found in the blood. If any had been missed in the patient exclusion phase then with as many subjects as this (260?) and with the best techniques available being used, you'd have thought if present then at least some cases would have been picked up, but instead we have zero. Borrelia as a cause therefore looks pretty unlikely now, though some other bacteria being responsible is yet to be ruled out as i understand it. It'll be interesting to see if they find anything, or not.
     
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