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PANDAS rabbit hole

Discussion in 'General ME/CFS Discussion' started by Beyond, Sep 20, 2015.

  1. Beyond

    Beyond Juice Me Up, Scotty!!!

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    Probably this has been addressed before but lets see what happens...

    http://beverlyhillsshrink.blogspot.com.es/2012/03/adult-pandas-bare-facts.html

    According to this guy, not only streptococcal infections but also Lyme and a bunch of other infectious agents CAN precipitate an "adult PANDAS" (which would be ANDAS, no, it would be ANDACI: Autoimmune Neurological Disorder Associated with Chronic Infections). The guy says chronic infections cascading autoimmunity "nest" in the GUT, sinuses, tonsils and some more.

    I am going to test my ASLO and Anti-DNase B and if possible some more.

    This is to be taken into consideration as well:

    http://www.sciencedirect.com/science/article/pii/S0091674904001927

    In any case elevated ASLO/ASO might be a marker of autoimmunity in cases of chronic "mysterious", "somatic" or "psychiatric" health problems. Really intriguing!!

    I got prompted to review this before some guy on another chronic health problems forum came saying he was desperate after years of illness and he curiously had elevated ASLO which he assures remains a constant in test results. I am positive HE has "ANDAS", not so sure about me, since I had this clear mental picture of what started my autoimmunity, but is worth a shot since I do hace OCD and apparently everyone in my house is sick at this point.
     
    Last edited: Sep 20, 2015
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I will have to have a look at the papers you tagged after dinner but as a first off elevated ASLO/ASO is not a marker of autoimmunity. It is a marker of immune response to streptococci. Even in the studies that seem to show autoimmunity after streptococci the antibodies are against antigens that have nothing to do with the streptococcal antigens. I am deeply sceptical but always ready to read more!
     
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  3. Beyond

    Beyond Juice Me Up, Scotty!!!

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    Hmm you´ll need to put into context my alleged assertion in order to understand it. Read the abstract. I wrote that it appears to be an autoimmune marker when you have some kind of chronic immune -related disorder. Of course I understand in normal conditions it just means an streptococcal infection. I just found significant that it might very well be that in some adult autoimmune patients there are elevated antibodies for strep and this ties with the polemic PANDAS.

    Some people with elevated ASO or/and or Anti-DNase B also present brain antibodies:
    .
    http://onlinelibrary.wiley.com/doi/...nticated=false&deniedAccessCustomisedMessage=

    This would be the basic rationale of the whole thing anyway, is just an hypothesis. Do you think this is a coincidence? It is great to have a real doctor discussing stuff in any case.

    I don´t even know if this is relevant in the CFS scenario (although it looks like?) or my specific case, but as I said in the OP I was prompted to pursue this when I saw that a guy with the typical "chronically fatigued-mysterious disease" posted some test results and his ASO was quite high.

    Something started the autoimmunity/inflammation loop that is affecting the CNS causing bizarre symptomatology, infections are a good candidate, and the gut a key place. It is crystal clear in my case at least that an specific agent started the loop. The body does not forget how to sleep or how to process food without attacking your own tissues from one year to the other. Its like acquiring an informatic virus, and the computer is compromissed.
     
    Last edited: Sep 20, 2015
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  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    The main article you quote looks like drivel to me. This is not immunology. It is picking up immunological fag ends and stringing them together to sound like immunology. It is hard to know where to start but the real problem is the basic assumption that rheumatic fever and post-streptococcal infections are autoimmune. We have little or not reason to think that - it is just that this idea was made fashionable in the 1960s and stuck. The ASLO antibodies are against the strep, not the self. The presumption that they 'cross react' has never been shown to be so. In the model Mady Hornig used I think they did find some autoantibodies in their mice (and these are nice not humans) but they were to complement components which as far as I know bear no relation to streptolysin O. Antibodies to basal ganglia were fashionable for a while in the context of post strep disease but I am told that the guy who invented the test now no longer uses it - presumably because he has realised it is meaningless. In the neuroimunology world I think this has all blown over and been shown to be hot air.

    That may sound like establishment dogma but actually I am extremely anti-establishment in my views of autoimmunity (the idea that infections like strep cause autoimmunity remains the establishment position despite no evidence). I just like science to be based on clear thinking and evidence. The fact that the paper you quote was rejected by a journal is hardly surprising. It is just shoddy from start to finish.
     
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  5. Beyond

    Beyond Juice Me Up, Scotty!!!

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    You know, that kind of "content" is abundant on the Net. Many charlatans and fiction-writers are here. So it might be as you say. I have extensive experience with "drivel" online, and have created it myself more often than what I would like to think. We are kind of shielded online.

    Interesting information. Very valuable to have your grounded perspective on this.

    I guess I will get those antibodies tested and see if anything of this makes sense lol

    Hope this is not too vague of a question, @Jonathan Edwards but if you are against the hypothesis of post-infectious autoimmunity which are in your opinion more likely culprits? I was exposed to aluminum during two years in which I started showing autoimmune symptoms such as Dermatitis.
     
    Last edited: Sep 20, 2015
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  6. warriormom

    warriormom

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    Dr. Edwards, I'd like your thoughts on the molecular mimicry hypothesis with respect to Rheumatic Fever and it's manifestations.

    http://www.sciencedirect.com/science/article/pii/S0531513105017188


    Rheumatic fever is an autoimmune sequelae of a group A streptococcal infection where immune responses against host tissues play a role in disease pathogenesis due to mimicry with streptococcal M protein or N-acetyl-β-d-glucosamine, the immunodominant epitope of the group A carbohydrate. Both antibody and T cell responses are involved in disease pathogenesis, and human monoclonal antibodies and T cell clones have substantiated the mimicry hypothesis in carditis and Sydenham chorea, both prominent manifestations of rheumatic fever. In carditis, evidence suggests that antibody against the group A carbohydrate reacts with the valve endothelium potentially promoting inflammation and up-regulation of vascular cell adhesion molecule-1 (VCAM-1). The inflamed endocardium then attracts activated T cells which extravasate into the avascular valve and promote a Th1 cytokine display leading to eventual scarring and heart murmur characteristic of rheumatic carditis. The mimicry proposed between streptococci and heart has been linked to the autoantigen cardiac myosin and related proteins. The Lewis rat has been developed as a model of streptococcal M protein and cardiac myosin-induced valvulitis with delineation of the epitopes involved in the A and B repeat regions of streptococcal M5 protein and in the S2 and LMM regions of cardiac myosin. In humans with rheumatic carditis, T cell clones from peripheral blood and valves recognize epitopes of streptococcal M protein and human cardiac myosin, as well as other alpha-helical proteins present in the valve. The hypothesis of mimicry and epitope spreading may explain how cardiac myosin, an intracellular protein in myocardium, can lead to T cell mediated valvular heart disease. Distinct epitopes of cardiac myosin and M protein have been defined which are associated with rheumatic carditis worldwide. In Sydenham chorea, antibodies which recognize ganglioside and N-acetyl-β-d-glucosamine target the neuronal cell surface and lead to antibody mediated cell signaling and dopamine release which may lead to the movement disorder. In this overview, rheumatic fever pathogenesis has been defined based on mimicry and autoimmunity, but there are yet many other parameters which contribute both genetically and environmentally to this globally devastating disease in children. The challenge is to discover them in the years to come.
     
  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    This sort of report sounds all very plausible but as I understand it there is in fact no consensus that anybody has found convincing evidence of mimicry. Scientists often going on doing experiments until they find evidence for what they assume to be the right theory at the start. There is a give away here too. The suggestion is that the mimicry is 'substantiated' by 'monoclonal antibodies' and 'T cell clones'. And that is no good. You cannot quantitate monoclonal antibody levels in a patient or T cell clones. You grow up these from patient material and the problem is that if you try hard enough you will grow them from everybody. Substantiation would need to come from conventional antibody level tests or T cell responses using unselected T lymphocytes. The fact that this is not given as evidence pretty much convinces me that there is none.

    Moreover, there are all sorts of problems even if the T cells against heart valves were there. It would not explain the arthritis or the rash - and the rash is a transient diffuse erythema quite unlike anything produced by T cells. And if this really was an autoimmune disease it ought to go on producing signs for years and the reality is that active rheumatic fever lesions last a few days or perhaps a week or two. After that you have scarring fibrosis causing gradual stenosis of the mitral valve. In fact the autoimmune/mimicry theory is completely crazy as an explanation of the real disease - but it is amazing how simple minded scientists can be. Once a theory has become dogma.
     
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    There are no culprits. That is clearly indicated by the fact that autoimmune diseases in the great majority of cases show random epidemiology. There are no epidemics or geographical variations. (There are a few exceptions and ME might be one.) As indicated in a previous thread the simpler answer is that autoimmunity arises as a random 'crash' in a complex regulatory system due to random generation of antibody molecules that can cause a loop in the 'software'. The details are very complicated but the specific signal pathways involved have been discussed in a variety of review articles by myself and others. Basically there is nothing to suggest that something in the environment 'triggers' autoimmunity - and a lot to suggest that nothing does in most cases.
     
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