BurnA
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I have not read the paper yet .....
Just wondering if you got the chance to read this paper in detail yet and if you had any additinal comments to make ?
Thanks
I have not read the paper yet .....
@Jonathan Edwards was this the EMERG meeting you attended today?I think it will happen. Various relevant people will be meeting in a fortnight's time.
How are your symptoms now? Did you or do you have other symptoms from your pots/oi? If so, did it help those as well?I started taking this combo a couple of weeks ago:
250 mg CDP-choline
300 mg Pantethine
6 eggs daily (LOTS of choline in the form of phosphatidylcholine)
Also 1 g biotin, although I don't know if this has contributed to my success
My RHR has decreased from the mid 90s to the mid 70s. Also my HR seems less reactive and is less prone to suddenly swing.
I should start my own thread but I just wanted to chime in to say that in my case cholinergic supplements have helped my autonomic dysfunction.
@Jonathan Edwards was this the EMERG meeting you attended today?
Yes, we discussed replicating the antibody findings. It is just a matter of logistics - the sort of logistics t
hat the meeting was set up to capitalise on.
I have finally managed to look at the paper. The antibody findings look interesting but the difference between patients and controls does not make me think these are pathogenic antibodies actually causing symptoms. A proportion of controls had similar levels to patients -a smaller proportion, but not an order of magnitude smaller as far as I can see. This looks more like an indirect signal of some autoimmune process.
Glad to hear you participate in these things professor
Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine at University College London (UCL), has agreed to advise us on all aspects of the trial. He is known worldwide for his work in B cell immunology and as lead researcher in the clinical trials of Rituximab for rheumatoid arthritis. No UK expert is better placed than Professor Edwards to advise us on setting up a rituximab trial for ME patients.
You can read his statement on the trial here.
The antibody findings look interesting but the difference between patients and controls does not make me think these are pathogenic antibodies actually causing symptoms.
What might elicit a response would be epitopes that have undergone post-translational modification during cell death. But since cell death is going on all the time in an active thymus this is a bit hard to predict.
Interesting idea, but why would it happen in some people and not others?Might then the triggering of autoimmunity arise from a normal cellular protein being cleaved by a viral protease, and then that protein escaping the cell during lysis?
And if so, if viral protease cleavage of cellular protein can in principle trigger autoimmunity, might this be where we could search for possible causal connections that link a specific viral infection to the specific autoantibodies found in the infected person?
Let me illustrate what I mean by an example: in the case of the muscarinic receptor autoantibodies found by Fluge and Mella, suppose we find that in a common ME/CFS-associated virus (like say enterovirus) there is a particular viral protease that is able to cleave the muscarinic receptor protein, and thus cause post-translational modification to this protein.
Let's say hypothetically we find that this viral protease is not able to cleave many other cellular proteins, but we observe it can cleave the muscarinic receptor.
So then we may start to think that this is more than a coincidence, and that the muscarinic autoantibodies found may be a direct result of the viral protease cleaving the muscarinic receptor protein.
You mean like dialysis?A fast but expensive way to demonstrate possible autoimmune problems is to filter the blood. There are machines that do that. I do not know the details with respect to antibodies though, nor the side effects. I believe costs are high.
A fast but expensive way to demonstrate possible autoimmune problems is to filter the blood. There are machines that do that. I do not know the details with respect to antibodies though, nor the side effects. I believe costs are high.
Yes, like dialysis, but there are other versions of the technology. I do not know all the details, its nothing I have investigated properly.You mean like dialysis?
Yes, like dialysis, but there are other versions of the technology. I do not know all the details, its nothing I have investigated properly.
Would be technically possible to experimentally inoculate ME/CFS patients with recombinant muscarinic or recombinant adrenergic receptors, to act as a decoy antigens (sacrificial target antigens) for these autoantibodies?
Such decoy antigens should mop up the autoantibodies, and if these autoantibodies were driving ME/CFS symptoms, you might expect the symptoms to improve very soon after the decoy antigens are injected.
Might such a procedure help determine if these autoantibodies are functional or not?
Might then the triggering of autoimmunity arise from a normal cellular protein being cleaved by a viral protease, and then that protein escaping the cell during lysis?
And if so, if viral protease cleavage of cellular protein can in principle trigger autoimmunity, might this be where we could search for possible causal connections that link a specific viral infection to the specific autoantibodies found in the infected person?
Let me illustrate what I mean by an example: in the case of the muscarinic receptor autoantibodies found by Fluge and Mella, suppose we find that in a common ME/CFS-associated virus (like say enterovirus) there is a particular viral protease that is able to cleave the muscarinic receptor protein, and thus cause post-translational modification to this protein.
Let's say hypothetically we find that this viral protease is not able to cleave many other cellular proteins, but we observe it can cleave the muscarinic receptor.
So then we may start to think that this is more than a coincidence, and that the muscarinic autoantibodies found may be a direct result of the viral protease cleaving the muscarinic receptor protein.
As indicated somewhere above, the difference in levels of antibodies between controls and patients in the recent study does not look to me to indicate that what is being measured is pathogenic. In the autoimmune diseases where we think antibodies are pathogenic the differences are much more clear cut.
So there must be some other undiscovered pathogenic antibodies?
I'm obviously not an expert but I can't help feeling that the observed changes (in levels of autoantibodies) are secondary to the main disease process i.e. knock-on effects. A useful starting point perhaps, in terms of identifying immune dysfunction, but I think we still need to look a lot deeper. I think we need to be careful to avoid giving undue importance to the first glimpses of abnormalities, as important as they are, so that we don't get stuck down blind ally ways. But that's not to downplay the importance of the research.As indicated somewhere above, the difference in levels of antibodies between controls and patients in the recent study does not look to me to indicate that what is being measured is pathogenic. In the autoimmune diseases where we think antibodies are pathogenic the differences are much more clear cut.
As indicated somewhere above, the difference in levels of antibodies between controls and patients in the recent study does not look to me to indicate that what is being measured is pathogenic. In the autoimmune diseases where we think antibodies are pathogenic the differences are much more clear cut.
AUTO-ANTIBODIES FOUND IN ME/CFS AND ITS COMORBID CONDITIONS
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AUTO-ANTIBODIES ME/CFS POTS ORTHOSTATIC SJOGREN'S
OBSERVED HYPOTENSION SYNDROME
——————————————————————————————————————————————————————————————————————————————
Adrenergic receptor alpha 1 Yes
Adrenergic receptor alpha 2
Adrenergic receptor beta 1 Yes Yes
Adrenergic receptor beta 2 Yes Yes Yes
Muscarinic receptor M1 Yes Yes
Muscarinic receptor M2 Yes Yes
Muscarinic receptor M3 Yes Yes Yes
Muscarinic receptor M4 Yes
Dopamine D2 receptor Yes
Mu-opioid receptor Yes
Serotonin 5-HT1A receptor Yes
Serotonin (neurotransmitter) Yes
Microtubule-associated protein 2 Yes
Phosphatidylinositol Yes
Insoluble cellular antigens Yes
Cardiolipin Yes
Heat shock protein HSP60 Yes
Anti-citrullinated protein Yes
I do not see why this should be a way to autoimmune disease. If antibodies are formed to the cleaved fragment that might be a good extra way to target the infected cells. Other cells would not suffer since they had no cleaved fragment on them.
Yup. I've been talking with someone from dysautonomia international and they think ritux does best in pots and oi. So I'd say you hit the nail on the head there! Some of the side effects of rtx scares me, but dysautonomia international is looking at different things for the antibodies and I hope something less toxic than rtx!Muscarinic and adrenergic receptor autoantibodies have been found in POTS and orthostatic hypotension (which are both listed as ME/CFS autonomic dysfunctions in the Canadian consensus criteria), and these autoantibodies have also been found in Sjogren's syndrome (which may be more common in ME/CFS 1).