Discussion in 'Phoenix Rising Articles' started by Phoenix Rising Team, Feb 20, 2013.
Are you sure levamisole decreases autoantibodies? I thought it was the opposite.
Hello to everybody,
As many of you, I'm trying to fully understand the mechanism proposed in the recent publish paper from KDM et al.
I've read all your comments and reports, and they are great, but they seem not to address a few issues that for me, are the most important things to understand. So, I am going to write down the questions that I am not able to solve, with the target of being able to explain in very simple words the proposed mechanism, mainly for the Spanish CFS community, who mostly does not manage in English, and are eager to know what is all this about.
The whole study is very well summarized here:
(thank you Joel for the great article!)
My goal is to complete /correct the following sketch:
(it's just an ugly-fast made drawing I made while reading the article and researching, but it'll be "nicer" when finished!
pDCells express HERVs genome, transcribing HERVs' proteins (gag and env). They don't say, but I assume that they go to the cytoplasm after being transcribed, where they may act as superantigents, that after being processed by phagocytosis will create the HLA-DR (MHC II) membrane receptor, that distinguishes the Antigen Presenting Cells from the rest (APCs). But this process is carried out in an abnormal way, so that the Lymphocytes T that stick onto these receptors in order to be activated, and thus are"told" what antigen to attack, are improperly and non-specifically activated. A lot of lymphocytes are activated by this way, then they activate in turn lymphocytes B that will synthesize antibodies against HERVs's proteins.
2- Where do these antibodies go?:
a- To the cell membrane of the pDCs? If so, do they die, or are just wrecked as a response, b/c the lymphocytes attacking those antibodies are not efficient due to the "non-especific activation"? The immunohistochemical assay shows that only pDCs shown reactivity against HERV proteins, so the only way this can happen (that I know), is if in their membrane, they express antibodies against HERV proteins. To my knowledge, this may happen independently of whether gaga and env proteins are only inside the cell or also in the serum.
b- To the HERV proteins, provided they go out of the cell. Do they? this is important in the sense that these proteins could travel throughout the whole body, so, they could be attacked in any place, explaining a systemic immune activation: systemic inflammation, coming from the gut! (this is the main idea...).
c- To ANY free protein in serum or inside cells that resembles the HERVs' proteins. This is the basis of molecular mimicry, and this is actually the way that it's proposed for the origin of autoimmunity, that is, lymphocytes and other members of the acquired response would attacked self proteins or self cells, in ANY part of the body.
Moreover, if we have a bunch of Lymphocytes "trained" to attack ANYTHING with antobodies against HERVs' proteins, they would attack ANY cell expressing these proteins...
So, in short, based on the above, this is my main question:
Where do the antibodies against HERVs' proteins go?, and what would be the exact process by which they are responsible for the autoimmunity? (Some of the possibilities I have listed above? A combination?)
2- Last question: they explain that the humoral response (Th2) against the HERVs' proteins leads to autoimmunity through molecular mimicry. Ok, the process I have described, if I have got it correctly would be exactly this, what would explain a shift of Th1 to Th2. So then, we would have two pathways that could cause symptomatology:
- Deffective Th1 response b/c of improperly activated lymphocytes T, and
- Excess Th2 response by the process I've explained of molecular mimicry involving antibodies anti- HERV proteins, and directly by the effect of dysrupted pDCs: low NKs, inflamation, etc.
So, the last quesion: What are the mechanism that wrecks the normal function of pDCs in the first place? I have assumed there may be two ways: 1- the improper Antigen Presentation process and 2- the attack of pDCs by lymphocytes.
I would really appreciate if any of you could help me with all this questions. More than one brain think better than only one (especially if layman and brain fogged!).
I, of course, do not have the knowledge to understand all this on my own, and would like to apologize beforehand for taking the risk of trying to understand things that are beyond my knowledge (that's why I'm asking to more expert people).
Thanks in advance for your insights!
Hello everyone. I brought this up before: ok, viruses, but so many of kdm's patients are testing positive for borrelia. This is not a virus. It's the result of a tick.
How does this connect to all this?
Or is it that we all have borrelia from time immemorial and our immune system keeps it down, and when sick with CFS-me, the latent infection surfaces.
I am having some difficulty with this, particularly having seen folks with true Lyme.
Thank you for taking the time to answer my questions.
Helene - I've tested negative for Borrelia via KdM - dont know what the actual %age of his patients test positive.
Good morning to you all,
Well, I was tested at igenex, and neuroscience and these were inconclusive. KDM tested and I was negative ( twice). He suggested infectolabs, and it came out positive. I know of several other folks in this category.
Thanks very interesting - seems that some lab testing is a waste of time then? Were your first tests with KdM done at Redlabs?
I wonder how to reconcile those older abstracts with the reports in the past two years about levamisole causing increased autoimmune skin diseases when it was used as an adjuvant in cocaine. They seem to be contradictory.
Either way, levamisole sure sounds like nasty stuff. I'd like a way to reduce autoantibodies but wouldn't touch this stuff with a ten foot pole!
Thanks for the links!
Low dosis and high dosis have opposite effects.
In 2009 dec. I was tested at igenex. On the basis of that a couple of doctor's suggested possibility of Lyme, but the tests were inconclusive really. Then in 2011 and 2012 I was tested at redlabs, and the tests were negative. KDM suggested the lab in Germany. These tests were done relatively recently, and they came out positive with an active infection. I present as classic CFS.
I really do not know how to put all this together. Several KDM patients who were classified as ME are now positive for borrelia and/or other associated confections.
If anyone can shed any light, please do
There is a lot we don't know yet, but I find it very interesting that plenty of people test positive for Lyme, often patients are very surprised, often they have had negative results previously.
I have lots of thoughts on Lyme and Borrelia and am going to be covering it in my next Zoonotics article (here is the intro to that series). There is a lot to talk about there and plenty of research papers for me to read through first.
It is not impossible for Lyme/Borrelia to be a cause or a component of ME/CFS. We have not done enough to rule it out yet, though we have taken some steps on that road, which is good. On the other hand some people may have Lyme, but think that they have ME/CFS. Everyone should be tested in my view. How much and what tests is still something I am researching. Finally, there is no rule to say that someone with ME/CFS cannot have Lyme/Borrelia as a coinfection, even if it is not a cause of their ME/CFS, and given the immune disfunction in ME/CFS that may be a reason why some people cant get over Lyme even when treated.
Similar story with other infections like Bartonella, Babesia etc.
Helene, may I ask did you do the western blot igg and igm at Infectolab or the Ltt elispot, or perhaps both? I did the ltt elispot at infectolab which came out negative. Don't know whether should do the western blot too to be sure, just more money to pay out...
Is this suggesting that if the changes in the gut flora are corrected (I take it gut flora changes means too much bad bacteria?) this could bring benefit/resolve the subsequent immune problems? is this why some find correcting gut helpful? is it suggested that gut treatments are important?
Leachim shared above that 'De Meirleir's model of the disease process starts with disruptions in the gut flora causing an array of immune dysfunction'. Does KDM believe then if the gut is treated at the start of the illness the downstream processes can be stopped and these few patients if caught early enough can make good recoveries? I know of one young woman who hadn't been ill for long, saw kdm, followed his gut treatments and made a full recovery. Dont know whether it lasted. Know others ill longer, saw KDM, did his gut treatments with little to no benefit.
Yes bad bacteria, but also potentially other pathogens and toxins. There are other people on here with more experience of the gut than me. My own gut is generally good. It was bad at first then got better and the last month has been a little off again, but not as bad as before. I am waiting on test results though as I am told that your gut can be a mess even if you dont get lots of symptoms, so maybe mine is a mess. Dont know yet.
I think the paper is suggesting that the better state you can get your gut in so that it is functioning well and with the minimum of inflammation then the lower your expression of HERV proteins. HERVs aside, as you say, some people have had improvement by getting their gut right so worth trying in that area I think. Like you say though, some people still have problems even if they improve that area. I think as a general rule the longer your illness the worse your chances, but thats just my personal view. I may be wrong about that.
In the case of HERV expression, I dont know if fixing your gut would stop HERV expression altogether, and resolve the immune problem(s), but I think this paper, and other papers talking about HERVs, are saying that you should have less of a problem at least.
I'm going to be paying close attention to my gut test results and trying to improve there in any way I can.
Yes, they are very very expensive. I suggest you write to them and ask just what you asked me. That is, can there still be a positive with the other tests.
I did the whole set for borrelia, as well as two other infections.
But what does KDM give for the gut. Arabinogalactan. Daosin. And of course, antibiotics to kill of bad bacteria.
I have been interested in fecal transplants for this reason you all site regarding the gut. Dr. Broody in Australia has had some success with CFS using fecal transplants.
Two Canadian doctors have just invented synthetic feces for fecal transplants and this will be extraordinary. But it is. It widely available. And only to Canadians, and only for reclctrant cdifficile.
Fixing the gut is hard, I have found, and probiotics have not really lived up to expectations, at least the ones readily available.
The question that comes to my mind is WHY - we all have HERVs, so why do some people react to them and not others. This is similar to EBV - most people have EBV, so why do some people have reactivations and not others. So this is just another symptom.
Also very small study, and still needs to be replicated.
Not impressed at this time. (Although well written article!)
He also gives other things to individual patients depending on tests.
You can also try a Google Site Search
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