Angiotensin II type 1 receptor autoantibodies in POTS (2018) Yu et al

[Snowdrop]

This is related to ME but I didn't see where else this might belong. So it's here:

https://www.ncbi.nlm.nih.gov/pubmed/29618472

I would like to have some thoughts on this research if anyone is able.
@Jonathan Edwards perhaps?

POTS is such a huge co-morbid issue for many of us.

Though I suppose there is a line of thinking that if a treatment comes available for ME and people get well does that mean it is treating POTS? Then I get confused.

 

[Melanie]

if a treatment comes available for ME and people get well does that mean it is treating POTS?

I don't think so. I don't have POTS but low BP and need Fludrocortisone. I also fainted on a Tilt Table test years ago. Due to using Minocycline in the past, I now have dizziness and unsteadiness although from time to time would experience these anyway.

I think so much goes wrong with ME (or CFS or SEID) that the main issue impacting all of us meeting the different criteria, I believe, is the metabolic issues Dr. Davis has found. But then there are the co-morbid issues which are many and are seperate diseases in of themselves and they would have to be addressed separately. POTS will have to be managed separately.

For me, now that the LBP issue is "set-in", I think I will always need to be on Fludrocortisone to help manage it.

Then, the neurological issues would need to be addressed separately. I don't think the treatment of the Metabolic part of the disease will resolve this as I think for the most part the damage is done.

 

[Snowdrop]

Thanks @Melanie for your response.

 

[Jonathan Edwards]

I have a specific worry with this study. It seems they have found antibodies to angiotensin receptors in most POTS cases. But they have also in the past found antibodies to adrenergic receptors in most patients. They state, as must be true that some patients have both - apparently quite a lot of them.

Contrast this with an established autoimmune disease, scleroderma. In scleroderma all patients have antinuclear antibodies to one or other of three antigens: topoisomerase-1, centromere or RNA polymerase. The key piece of evidence suggesting that the autoimmunity is causing the symptoms is that none of the patients have antibodies to more than one antigen. That makes sense because scleroderma is rare and to have antibodies to two antigens would effectively mean the person would have two causes of scleroderma - two doses of the same rare disease.

In general we do not see people with autoimmune disease having two types of autoantibody that are xpected to do the same thing. There are associations with unrelated antibodies like thyroid antibodies but that is different.

Put in ordinary terms when a car does not start you expect either the battery is flat or you have run out of petrol. A call-out mechanic does not expect to find both are the case in most cases.

So the presence of two different antibodies often together, actually makes it less likely that either are actually causing the problem. If the authors understand this sort of background to autoimmunity (which is partly common sense) they should explain in their discussion why they have this odd result.

Unfortunately most reports of autoantibodies like this turn out not to be repeatable. The overlap makes me think that more than likely here.

 

[Gingergrrl]

In general we do not see people with autoimmune disease having two types of autoantibody that are xpected to do the same thing.

Can you explain this further b/c in Hashimoto's Disease (at least in my case), I have both autoantibodies, TPO and TGAb. There are other autoimmune diseases like LEMS in which a person could have both the P/Q type and the N type Calcium Channel autoantibodies. Would these be exceptions to that rule or do these autoantibodies each do different things vs. the same thing?

Because if they did different things, it might be the same in Autoimmune POTS, meaning that the beta-adrenergic and the angiotensin receptor autoantibodies are doing something different (so some people might be positive for one and others might be positive for both)?

 

[Lisa108]

In general we do not see people with autoimmune disease having two types of autoantibody that are xpected to do the same thing. There are associations with unrelated antibodies like thyroid antibodies but that is different.

Put in ordinary terms when a car does not start you expect either the battery is flat or you have run out of petrol. A call-out mechanic does not expect to find both are the case in most cases.

To stay with that example, I'd say that the autoantibodies are not doing the same thing. They are both slowing down the car but by two different pathways. Having one would be bad, having both would be worse...

I think that many patients with Lupus erythematodes have more than one autoantibody.
The risk of developing Type 1 diabetes is higher in kids with more than one autoantibody against islet cells.

edited for clarity

 

[Jonathan Edwards]

The situation is complex but i will try to be specific.

Thyroid antibodies are a well recognised exception. They are very common in healthy people and more common as asymptomatic associations with things like RA. Because they are so common ( maybe 1 in 5 normal people) it is not unexpected that some people have both (maybe 1 in 25 would be expected). There is also probably a connection between the mechanisms that trip both antibodies relating to the fact that both antigens bind thyroxine.

I do not know abot the channelopathies but having spoken to Angela Vincent my impression is that the tests for these antibodies are easily overinterpreted and not yet fully validated.

Lupus is unique amongst autoimmune diseases in having lots of autoantibodies together i he same person. But we know why this happens. The immunopathology centres around complement dysfunction and that in itself is a means of generating a whole slew of autoantibodies.

The point about the car analogy is that we are dealing with rare events. Only a tiny percentage of the population have POTS. To have two causes of POTS would be vanishingly unlikely unless they two were linked in some way. I know of no immunological reason why antibodies to two different families of receptors,with different ligand should be linked. It is possible but my years of experience with papers reporting antibodies like this has made me sceptical. Most turn out to be unrepeatable.

 

[Snowdrop]

Thank-you @Jonathan Edwards for some very clear and thoughtful explaining.

I don't know if this will make a difference but I think (not sure) that the paper I linked to is a repeat study to validate another from 2014 here: https://www.ncbi.nlm.nih.gov/pubmed/24572257

It seems to be a small study. I have no ability to evaluate this or the other study to draw any conclusions though I suspect that the studies are limited and therefore difficult to draw too many conclusions of a positive nature?

 

[Jonathan Edwards]

I don't know if this will make a difference but I think (not sure) that the paper I linked to is a repeat study to validate another from 2014 here: https://www.ncbi.nlm.nih.gov/pubmed/24572257

The 2014 study is about antibodies to adrenergic receptors as far as I can see. If you find autoantibodies like this that you think might cause an illness then to validate the finding you would normally test for other antibodies with your assay system in order to show that they are not there and therefore that your first finding was specific. If you look for another sort of antibody and your system shows up positive for that as well the main conclusion would be that the assay system is non-specific and unreliable.

In other words the finding of positive results for other antibodies reduces the validity of the first finding.

The psychology of this worries me. Normally nine out ten laboratory experiments show nothing much. When you find an experiment gives a really interesting and potentially important result, as with the 2014 study, you keep doing the same experiment again and again because it is such fun getting consistently interesting results. All you have to is vary the experimental plan a bit each time and you can publish papers one after another without having to scratch your head to have another brilliant idea. If you really believe your results this is the obvious thing to do. So there should be two papers from 2015 and three from 2016 all confirming how reliable the first study was.

But if you are not quite sure you believe your results you prefer not to repeat them because they might turn out not to be repeatable. Instead you test for something else. The current paper is testing for something else.