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New Swedish ME/CFS-study indicates autoimmunity

Discussion in 'Latest ME/CFS Research' started by Ninan, Dec 11, 2013.

  1. Ninan

    Ninan Senior Member

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    Brand new study indicates a possible autoimmune reaction that could affect mithicondrial function.

    Abstract

    Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide fromChlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

    Read it all here
    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081155
    NK17, MeSci, Tito and 5 others like this.
  2. SOC

    SOC Moderator and Senior Member

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    I admit that I don't understand half of the abstract, but it sounds like sound science (unlike a lot of the garbage we see in "CFS" research) with objective measures, sizable samples, and comparisons to healthy people and those with possibly related illnesses. It also fits what we know about the illness (again unlike some of the so-called research we've seen). This research looks very promising to me. :)
    aimossy, MeSci, jenbooks and 3 others like this.
  3. alex3619

    alex3619 Senior Member

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    From: http://en.wikipedia.org/wiki/HSP60

    My bolding.

    Mitochondrial function depends on imported and locally synthesized proteins. These have to be folded correctly to work. If something interfers with HSP60 then this process may be jeopardized.

    However it is unclear how an extra-cellular antibody could have an impact on an intramitochondrial HSP. It might if the HSP is imported from outside the cell, but I do not know this is the case.

    I think it likely this may be a marker of ME in some patients, but possibly not a cause. In any case its very interesting.
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  4. alex3619

    alex3619 Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/20159025

    Life Sci. 2010 Mar 27;86(13-14):499-504. doi: 10.1016/j.lfs.2010.02.010. Epub 2010 Feb 14.
    Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of small intestinal epithelial cells.
    Takada M, Otaka M, Takahashi T, Izumi Y, Tamaki K, Shibuya T, Sakamoto N, Osada T, Yamamoto S, Ishida R, Odashima M, Itoh H, Watanabe S.


    HSP60 protects the gut lining from salicylates and hydrogen peroxide There is an implication here. but far from proven, that HSP60 inactivation by antibodies might lead to decreased gut lining integrity.
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  5. alex3619

    alex3619 Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/21508342

    Arterioscler Thromb Vasc Biol. 2011 May;31(5):960-8. doi: 10.1161/ATVBAHA.110.217877.
    Heat shock protein 60 and immune inflammatory responses in atherosclerosis.
    Grundtman C, Kreutmayer SB, Almanzar G, Wick MC, Wick G.

    This paper is a sample of some of the research. HSP autoantibodies may attack a range of endothelial cells, which might mean both gut and blood vessels.
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  6. aimossy

    aimossy Senior Member

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    Thanks @alex3619 :)
    Wonder what prof will make of this. Does anyone know how to put the link of this to his thread. Just a thought.
  7. aimossy

    aimossy Senior Member

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    Thinking about human heat shock proteins and the hypothalamus now as well so looks like a google search out of pure interest.
  8. Marco

    Marco Old blackguard

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  9. aimossy

    aimossy Senior Member

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    @Marco ........ME MOMENT hahaha!! I thought it was a new research paper that would support the one that was in that thread and didn't check!! doh:D:redface:.thankyou.
  10. Marco

    Marco Old blackguard

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    No probs. I had to do a double take myself just to be sure!
    aimossy likes this.
  11. Ninan

    Ninan Senior Member

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    Thanks Marco, I hadn't seen your post. Very interesting thread!

    I have an explanatory text from the authors, meant for patients since as SOC says, the study is not extremely accessable.

    Note that this is mine (and Google's) rather quick translation from Swedish. (And I'm a political science major, this stuff is rather new to me.) But most of it should be at least understandable.

    2013-12-03 Summary of article in PLOS ONE: The starting point when we started this work was the indications that ME could be an autoimmune disease. Partly inspired by some neurological diseases shown to be autoimmune (MS, Sydenhams chorea, Guillain Barre syndrome, etc), partly because of the Norwegian results with Rituximab (which of course affects antibodyproducing cells).

    I (JB) also had a basic idea that mitochondria could be affected. Partly because they are the main producer of the energy that is based on the use of atmospheric oxygen (aerobic energy production), partly because mitochondria are intracellular bacteria that originally was taken up by our cells for over a billion years ago. To get tired quickly is one of the most important ME symptoms. I draw the conclution from the research over the past few years that it is mainly the aerobic energy production that is affected by ME. Energy reserves takes longer to be replenished with an ME-sick than a healthy person.

    Mitochondria still have many bacterial properties. The immune response to a bacterial infection sometimes include antigens against human mitochondria and the infected bacteria. One example of this type of cross reactive antigen, which is found both in mitochondria, parasites and bacteria, is the heat shock protein 60 (HSP60). HSP60 is called a chaperon. In French and English chaperon means apron. Chaperons settle around other proteins and help them fold properly. Proteins are originally created as long threads. They must then fold into a three-dimensional structure to be able to work. HSP60 can thus influence the behavior of many different proteins, above all in the mitochondria where HSP60 originally belongs. If the HSP60 is prevented to perform its chaperon function, for example by antibodies that bind to it, many other functions in the body might be affected.

    Now to our results. We first studied antibodies against HSP60 in ME patients and healthy control subjects (blood donors), and found that patients with ME often had higher levels of such antibodies. Then we divided the HSP60 in many small parts, so-called synthetic peptides. It turned out that only certain peptides binds to antibodies of ME-patients and controls. A special section, in the middle of HSP60, binds to antibodies from ME-patients more often than to antibodies from the controls. They came from a special coil of HSP60, the one which is the most important for HSP60's chaperon function. One can imagine that such antibodies could prevent the chaperon function, but we did not study this. Further studies should look at whether such antibodies prevents HSP60 to act. We should also study whether such antibodies really affects the functioning of the mithicondria. We did neither in this study.

    The HSP60 peptide which reacted mostly to ME-the patients' antibodies came from Chlamydia pneumoniae (often called TWAR). Because HSP60 in humans and bacteria are so similar to each other this doesn't mean that it's been Chlamydia pneumoniae, that developed the antibodies. Further investigation is needed.

    Only 20-40% of the ME-patients had elevated levels of antibodies to HSP60-peptide. The antibody finds can therefore not be the only explanation of the disease. But our results are in accordance with the notion that ME is an autoimmune disease. Since ME often starts with an infection you can imagine that immune response to the infection in naturally predisposed individuals can provide an autoimmunity affecting mitochondria. It can be an important first step to define ME as an autoimmune disease. But as you understand very much research work remains before we can consider the explanatory model as established.

    We naturally hope that our findings will lead to a simple laboratory testing to diagnose ME to develop, but we are unfortunately, not there yet. Right now we are waiting tensely to other research groups will be able to reproduce our results.

    Jonas Blomberg, Björn Herrmann, Olof Zachrisson, Carl Gerhard Gottfries and associates​
    Last edited: Dec 12, 2013
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  12. Marco

    Marco Old blackguard

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    Thanks Ninan

    That's very comprehensible and perhaps additional detail that we could ask the Prof to respond to.

    Misfolding of proteins has been noted before in ME/CFS as has an attenuated heat shock protein response to exercise. Drugs that might address protein misfolding in a range of diseases are now being talked about :

    http://www.sciencedaily.com/releases/2013/12/131209181101.htm
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  13. Ninan

    Ninan Senior Member

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    Thanks for the link @Marco . Interesting! Let's hope they are on to something.
    aimossy likes this.
  14. alex3619

    alex3619 Senior Member

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    I started talking about protein misfolding in about 2000 or so. Its very clear that to fold properly often requires reduced glutathione, which has commonly been shown decreased in ME, especially the brain, and is often decreased in people with methylation issues.
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  15. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    If only the research establishment were properly open to disabled scientists, then you and I and other scientists with ME might have cracked it by now! Let us into those labs! :bang-head::bang-head::bang-head:
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  16. aimossy

    aimossy Senior Member

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    Im Confused:(.... alex in short said about the folding properly requiring reduced glutathione which has commonly been shown decreased in ME. im no science person but I thought that would mean our folding would be ok.
    I have probably thinking too simply or just confused.lol. can any of you two clarify for me?:)
  17. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I think by 'reduced' @alex3619 means the opposite of oxidised, rather than decreased. This page may clarify.
    aimossy likes this.
  18. alex3619

    alex3619 Senior Member

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    We have a decrease in reduced glutathione, but possible also total glutathione. Confused? The terminology is confusing. I don't want to get into the definitions as redox states can give me a headache sometimes, so I can only guess it will make things more confusing to most.

    A reduced molecule is the opposite of an oxidized molecule. Reduced glutathione means active glutathione, whereas when oxidized its inactive. In this case reduced glutathione is used to create things called sulfide bridges, which are substantially little ties to hold a protein molecule together in weird shapes.

    Edit PS What MeSci said. ;) When reduced glutatione is abbreviated to GSH, with the H being hydrogen. Oxidized glutathione loses a hydrogen, and two molecules join, and its abbreviated GSSG. The S is for sulfur (or sulphur many places, including here).
    Last edited: Dec 13, 2013
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  19. aimossy

    aimossy Senior Member

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    cheers @MeSci it means something completely different thankyou.I knew one of you would sort me out there:)
    edit :and @alex3619!
    yes I was thinking to simply but was suspicious I was and can see how anything deeper than what you two just gave me would cause a headache.
    I would donate to your home labs you two. hahaha. awesome! :D
    Last edited: Dec 13, 2013
  20. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I'm setting mine up right away! ;)
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