A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
Mark Berry presents the first in a series of articles on the 11th Invest in ME International ME Conference in London ...
Discuss the article on the Forums.

DAMPs and PAMPs and immune system dysregulation

Discussion in 'General ME/CFS Discussion' started by Snow Leopard, Jan 6, 2015.

  1. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,611
    Likes:
    12,417
    South Australia
    I noticed that Griffith University (Australia) had the following as a research project:

    See:
    http://en.wikipedia.org/wiki/DAMPs
    http://en.wikipedia.org/wiki/Pathogen-associated_molecular_pattern

    Along with this interesting hypotheses such as:
    "Dangers Within: DAMP Responses to Damage and Cell Death in Kidney Disease" (open access)
    http://jasn.asnjournals.org/content/22/3/416.full

    DAMPs have been suggested as possible risk factors leading to (regulatory) loss of control of antibody producing cells. There is also the possiblity of DAMPs themselves causing antibody independent feedback loops resulting in immune system dysregulation.

    I am a little skepetical, at least with regards to the role in CFS, but it seems like an interesting avenue.

    I am wondering what @Jonathan Edwards and others think about this?
     
    Last edited: Jan 7, 2015
  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,210
    Likes:
    31,615
    It all sounds very vague to me. Genetic polymorphisms in DAMP or PAMP receptors might alter thresholds for an inflammatory mechanism in ME/CFS but the weight of evidence is that there isn't much inflammation in ME. Polymorphisms might also change the threshold for an innate signal that could get tied up in an autoimmune loop - rather in the way that the DR4 Class II polymorphism facilitates anti-citrulline antibodies. But it does not say if they are looking at genetics. Otherwise I am not sure where you would put DAMP/PAMP in a pathogenesis cascade other than somewhere downstream just as mediators - and I am not clear quite what they would be mediating.

    The statement on severe immune compromise in ME seems a bit free-floating.
     
    Snow Leopard likes this.
  3. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,611
    Likes:
    12,417
    South Australia
    My personal hypothesis is that impaired cellular stress responses are involved in ME/CFS, in the absence of a strong inflammatory immune response (for reasons I will explain soon, hopefully). so I would actually predict a blunted DAMP/PAMP response. If autoimmunity is involved, then I would indeed expect it to be elsewhere.
     
  4. Marco

    Marco Grrrrrrr!

    Messages:
    2,369
    Likes:
    3,145
    Near Cognac, France
    I've no idea what they're proposing. If anywhere I'd be looking at a possible role for primed microglia over-reacting to a wide range of DAMPS/PAMPS which I believe is what Jared Younger is proposing with respect to his findings correlating leptin levels with fatigue. Leptin as far as I know hasn't as yet been identified as a DAMP/alarmin but its an emerging field and other signals relevant to 'energetics' such as ATP have.
     
  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,210
    Likes:
    31,615
    Yes, the problem for me would be why DAMP and PAMP responses suddenly malfunctioned when the disease started. I don't get a feel for any specific dynamics here.
     

See more popular forum discussions.

Share This Page