Discussion in 'Fungal Infection (Yeast, Candida)' started by osisposis, Aug 4, 2016.
aspergillus fumagatis disruptes the VDR , this is good and CFS and fibromyalgia plus,
What do you make of this alleged evidence for molecular mimicry @Jonathan Edwards?
I think you'll find your answer here.
Yup. This presentation is a load of nonsense. The guy starts with a few anecdotes and then babbles on about how many bacteria we have in our guts for about half an hour. There is no content here. The Congress on Autoimmunity is pretty much a joke institution set up by phoneys years back - still running.
I did not listen to the whole thing but if there is actually any coherent argument in there do let me know! There is no mechanism by which infection can cause autoimmunity by mimicry that I am aware of. If a bacterium can cause an immune response by mimicry then presumably the host itself can cause a response by being identical to itself, even more easily. It makes no sense.
I think the only argument was that since those proteins looked identical on the "supermicroscope", then -> molecular mimicry exists.
Your last point was great, kind of a nail in the coffin as far as the logic of molecular mimicry is concerned..
what do you think about this?
Guillain-Barré Syndrome Animal Model: The First Proof of Molecular Mimicry in Human Autoimmune Disorder
This is quoting work from Hugh Willison from nearly 20 years ago. Guillain Barre remains the one disease where it looks as if there might be a cross reaction with a pathogen. But note that the animal model is non sequitur - it proves nothing about what happens in the human. And whether there are really pathogenic autoantibodies in GB remains uncertain. And of course GB is very unlike autoimmune diseases where autoantibodies are well documented - it is a short lived monophasic process, even if recovery may be very slow and incomplete. If anything it seems to be the exception that probes the rule. I personally suspect it is more like rheumatic fever, where an antibody response to a pathogenic appears to throw up immune complexes with peculiar properties leading to joint and heart lesions. The idea that the immune response cross reacts with heart has never been substantiated and is almost certainly wrong.
That is interesting.
What you have to remember is that people are mostly like sheep. They have no new ideas so they just follow everyone else - they vote for Donald Trump or Mr Osborne's austerity despite both being close to suicide.
Immunologists are people and by and large they cannot think of any new ideas - or even work out which of the old ideas make sense - so they keep writing about an idea that is fifty years old and never made sense or was supported by any evidence.
This paper is drivel. The journal is of the sort that will publish anything anyone wants to pay for publishing (these days you pay journals to publish your stuff so they are happy to print nonsense and rake in the money.) There is actuually no experiment here. Moreover, the abstract is full of nonsense statements. Rheumatoid arthritis and lupus have nothing to do with mycobacteria. There might be debate about prevotella copra but at a rheumatology meeting of 3,000 scientists you are unlikely to find anyone who thinks it has anything to do with mycobacteria. The authors are just making things up as they go along.
What the paper shows is that if you walk on a beach and pick up a pebble, after five years of walking you are pretty sure to find another pebble that looks just the same. Or that if a child were to come up saying look I found two pebbles exactly the same you would conclude that God knew about the first pebble and made the second one to match. Put another way, if you drive two thousand miles you are bound to find two car number plates that are exactly the same apart from one number or letter.
What I think is hard for people to understand, and this is part of the reason why I post here, is just how bad most scientific papers are these days. This is the equivalent of some high school kids trying to work out whether there is a Higgs boson - without knowing any physics.
And what is so sad is that MOST immunologists, although they can see this is rubbish, cannot see why the molecular mimicry idea is rubbish, despite the fact that it is barn door obvious - and at least Marky90 gets it!
Our bodies are full of proteins. All the time these proteins are being slightly damaged and eventually cleared away once they are too damaged. Amino acids get oxidised or cross linked or glycated. And every self protein that has been slightly changed is now 'almost identical to self' and so if molecular mimicry worked our immune system would constantly be mounting immune responses to these damaged proteins that cross reacted with good proteins and gave us total autoimmunity every day of the week. It simply cannot make sense. And since there is essentially no evidence for an association between infection and autoimmune disease that would fit with mimicry nobody should be surprised.
So, the molecular mimicry idea is rubbish, but possibly true in the case of Gullain-Barre Syndrome (which can also be a chronic condition)?
My head hurts. I think I need to go lie down.
Molecular mimicry is rubbish as an EXPLANATION why autoimmunity should occur. It seems that cross reactivity may actually occur in Guillain Barre syndrome - presumably for some unique reason we so far have no clue to. (I.e. an exception that provides no reason to suggest cross reactivity is relevant to any other condition.) And Guillain Barre syndrome is not an autoimmune condition as far as we know. It is only chronic in the sense of the nerves being so damaged they do not recover. If there was a continuing immune response to nerves one would expect progressive deterioration and death.
I have to say that I am sceptical about Willison's claim to cross reactivity - which was blolstered very much by an animal model - but that proves nothing because you can always get animal models to mimic whatever you are studying if you inject them with enough nasty adjuvants. Demonstrating that patients had nerve damage because of antibodies against bacteria cross reacting with nerves is a much harder task. It has never been done for RA or most other autoimmune diseases. The only real proof we have that autoantibodies cause disease comes from neonatal lupus, myasthenia and Ro syndrome (congenital heart block) where the antibodies come from the mother.
The devil is in the detail.
I guess I feel I have to give Willison the benefit of the doubt because he invited me to write a chapter for a book of his!!
´Demonstrating that patients had nerve damage because of antibodies against bacteria cross reacting with nerves is a much harder task.´
Surely this, if proven, would qualify as autoimmunity, wouldn´t it?
´The only real proof we have that autoantibodies cause disease comes from neonatal lupus, myasthenia and Ro syndrome (congenital heart block) where the antibodies come from the mother.´
Now I´m really confused. If autoantibodies don´t cause disease, what makes patients with autoimmune diseases ill?
This is the chronic condition I was referring to: http://www.ninds.nih.gov/disorders/cidp/cidp.htm
Indeed, but my point was that it is extraordinarily hard to prove - in fact for ethical reasons more or less impossible because you would have to isolate the antibodies from a GB patient and inject them into a healthy person and give them GB. Scientists actually used to try this sort of thing on themselves decades ago but nobody does now.
You might say that giving rituximab and seeing improvement might be a good experiment - which is why I did it in RA. Remember that in RA when I did that experiment almost nobody believed that autoantibodies were causing the arthritis. They thought it was T cells. Trouble is that rituximab lowers more or less all autoantibodies so the fact that ones you are interested in go down does not prove they were the ones causing the trouble (this is the problem with the Charite/Bergen findings on antibodies going down in ME/CFS patients.) But at least if rituximab made GB better that would point in the direction of an autoimmune process. Whether that had anything to do with cross reactivity though is quite a different matter. There are so many antigens in a bug and so many in a man that it is not hard to find ones that seem to show cross reaction on ELISA plates.
Which brings us to this:
CIDP is a recognised chronic autoimmune neuropathy, chiefly with IgM antibodies as I understand it. It was one of the first conditions to be treated with rituximab successfully. But that is not Guillain Barre syndrome and as far as I know there is no evidence for it involving cross reaction with bacteria.
Remember that until we started using rituximab the word on the street in immunology was that autoantibodies did not do much at all except perhaps in lupus and myasthenia. And that was because there was so little to go on. Having shown that rituximab can make the clinical features of RA disappear with the antibodies there is now a more general acceptance that antibodies may be important in most autoimmune disease. However, you will still find most immunologists hanging on to the idea that bad T cells cause at least as much trouble (for reasons I never understood).
So yes, autoantibodies appear to cause these diseases but until recently an autoimmune disease was just one that was associated with autoantibodies and nobody was sure why.
And even now there are major holes in our theories. RA is associated with two unrelated autoantibodies: rheumatoid factor and anti-citrullinated protein. We have no way of knowing whether one causes the arthritis or the other - because both go down with rituximab.
What I was meaning for GB was that although there might perhaps be a cross reaction involved following an immune response to a bacterium we really need some other bit of explanation to indicate why this should occur with only one out o f thousands of bacterial species and one out of 40,000 human proteins. And that is the sort of thing that the explanation for RA that led us to rituximab was designed to address. It seems likely that for each of the rather few human proteins that gets hit by autoantibodies there is a specific flaw in the immune signalling language - a bit like a bug in Microsoft Word. It is likely that it GB is due to antibody mediated damage that there is a neural protein that has an 'Achilles heel' in its immune signalling capacities. It is still quite hard to see why this should show up when a similar foreign protein comes along, rather than just by chance anyway, but it is possible. The flaw is different for every protein targeted as far as we can see. And the way the flaw allows auto reactivity involves different pathways in each case. As a speculative example it might be that the neural protein binds to a receptor on T regulatory cells in such a way that it blocks the veto for self reactivity that applies to all other proteins, but this interaction with T regs only works in the presence of a cofactor from some campylobacter or whatever the bug is. That seems likely to be the sort of mechanism that applies in rheumatic fever except that it looks as if the subversive signal is via the complement system.
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