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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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Interesting, now we need the bond uni cfs guys to bump into them at a conference
This is not a surprise, its been suspected and discussed as far back as I remember on these issues. However, its the first time apparently that it has been demonstrated, and with more details as to why this happens.
The gene reassortment for antibody production has been known for a very long time. It was obvious there was a failure in suppressing replication of B cells that produce auto-antibodies in autoimmunity, but nobody knew the mechanisms.This reassortment is essentially a shuffling of genes in a very specific region. It is substantially random, though I think not entirely.
This helps our general understanding, and also reinforces the association between immune activation and autoimmunity, especially from pathogens. I do not think it immediately assists us with strategies for coping with this.
Bye, Alex
Just what I was thinking...nearly added that at the end of my post above.One area which is obviously under attack is the autonomic nervous system.... maybe the attack could be on the hypothalamus (isnt that what guides the ANS??)
Yes indeed.Im excited about this new discovery as I personally believe this may be part of the answer to our illness. At least even if ME/CFS research isnt moving forward much, other reseach which probably is relevant for us is.
Alex, if I read this correctly, it is saying that the key finding is that the failure occurs when the antigen (infection) is in a specific location, remote from the germinal centre, rather than being a widespread infection throughout the body, and that this is when autoantibodies may be created.
They also go on to mention "cross-reactive autoantibodies that can attack organ-specific targets" and "autoimmune conditions that target particular organs such as the heart or nervous system".
Is this aspect, which they seem to be saying is crucial, also part of what you say has long been suspected: that it must always be a localised infection that exposes the vulnerability to auto-immunity?
Does this also imply that auto-immune conditions will therefore always involve autoantibodies targeting specific organs?
And the main question I'm left with, from reading the article, is whether the specific organs that the autoantibodies attack will (typically/always) be the same organs that the original infection was localised to? Or different organs?
It seems that if this localisation aspect is key to autoimmunity, and if there is a predictable relationship between the organ affected by the initial infection and the organ affected by the autoimmune reaction, then the next question in any given (known or suspected) autoimmune condition would be to identify which specific organ is affected. If this is always the same organ as the organ affected by the initial infection, then there may be clues, both from the current symptomology and the history of infection, which help to identify the organ affected?
And in ME/CFS, I suppose the first guess would be that the organ affected would be the nervous system? Or some particular component of it?
Perovyscus mentioned Plasmapheresis on this thread http://forums.phoenixrising.me/inde...-alternatives-to-rituximab.18502/#post-309907
An important use of plasmapheresis is in the therapy of autoimmune disorders, where the rapid removal of disease-causing autoantibodies from the circulation is required in addition to other medical therapy. It is important to note that plasma exchange therapy in and of itself is useful to temper the disease process, where simultaneous medical and immunosuppressive therapy is required for long-term management. Plasma exchange offers the quickest short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be suppressed, usually by the use of medications such as prednisone, cyclophosphamide, cyclosporine, mycophenolate mofetil, rituximab or a mixture of these.
Wonder how that would go?
I wish B-cells would just develop a bad memory, like me.
In patients with autoimmune autonomic ganglionopathy, combining immunosuppressive medications prednisone and mycophenolate mofetil with plasmapheresis provides substantial and sustained clinical improvement that was not seen using either treatment alone. Multi-agent immunomodulatory therapies may be necessary to satisfactorily treat this immune-mediated disorder.
These studies suggest that combination therapy with IVIg may be effective for treatment of AMBDs. Rituximab can convert partial responders to high responders and these patients, once in remission, maintain a sustained prolonged clinical remission.
... Increasing attention is also being turned to the use of IVIg in combination with other agents, such as immunosuppressive agents or monoclonal antibodies.
Here is the paper by Chan and colleagues:
"Elimination of Germinal Center-Derived Self-Reactive B Cells Is Governed by the Location and Concentration of Self-Antigen"
http://www.cell.com/immunity/abstract/S1074-7613(12)00462-1
wondering if it would go the other way round, if IVIG or plasma exchange would convert partial Rituximab responders to high responders!? Hope Fluge et al have this on their radar !!