Dr Grubbs team ‘Strongly Suggests’ Autoimmunity in Dysautonomia

Belbyr

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https://m.medicalxpress.com/news/20...cEIxZZpxWlrJZGYfrTZfkmXEG6IGLB_QkTboDB42sJulk

https://www.ahajournals.org/doi/10.1161/JAHA.119.013602

Interesting Excerpt:

We have previously reported a comorbidity in POTS that could explain many of these clinical symptoms; platelet delta granule storage pool deficiency with diminished serotonin levels appears to be frequent in our experience.12 We have not proposed delta granule storage pool deficiency as an etiology of POTS; however, the deficiency might be acquired by autoantibodies, perhaps against enteric cells that produce serotonin in the gut that is stored in platelet granules.
 
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pattismith

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"Researchers screened the patients' blood for autoantibodies against nine receptors. A handful of patients showed elevated levels against all nine. But it was the prevalence of adrenergic A1 subtype receptor autoantibodies that make their findings so intriguing.


"I think that we have identified a biomarker. We now might have the ability to diagnosis this, or at least have an inkling. Like other autoimmune disease, we can take a blood sample and detect if there are increased levels of autoantibodies present. According to our results, autoantibodies against this particular receptor should be present in about 90 percent of patients with POTS," said Dr. William Gunning, a professor of pathology in the UToledo College of Medicine and Life Sciences, and the paper's lead author."

The problem with biomarkers is that the 10% of POTS people who are negative may be denied the diagnostic, like sjogren people who are negative for the more common sjogren associated antibody, doctors even neglecting the biopsy if the antibodies are negative, which is the contrary of what should be...
 

lauluce

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"Researchers screened the patients' blood for autoantibodies against nine receptors. A handful of patients showed elevated levels against all nine. But it was the prevalence of adrenergic A1 subtype receptor autoantibodies that make their findings so intriguing.


"I think that we have identified a biomarker. We now might have the ability to diagnosis this, or at least have an inkling. Like other autoimmune disease, we can take a blood sample and detect if there are increased levels of autoantibodies present. According to our results, autoantibodies against this particular receptor should be present in about 90 percent of patients with POTS," said Dr. William Gunning, a professor of pathology in the UToledo College of Medicine and Life Sciences, and the paper's lead author."

The problem with biomarkers is that the 10% of POTS people who are negative may be denied the diagnostic, like sjogren people who are negative for the more common sjogren associated antibody, doctors even neglecting the biopsy if the antibodies are negative, which is the contrary of what should be...
doctors will always find the means to do as little work as possible...
 

pattismith

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My one question and I could be completely wrong...

But, if these antibodies are so rampant in POTS & many CFS patients, why did the Rituximab CFS trials fail? Rituximab should have knocked out those bad antibodies, correct?
I don't know why some autoimmune diseases fail in Rituximab trials, but it happens.
But even in these diseases, there was anecdotal reports of rituximab success which is very confusing.
 

pattismith

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doctors will always find the means to do as little work as possible...
the fact is once they have a "biomarker" for 90% of people, they rely on it for the diagnosis. it is the same problem also with Ankylosis Spondylitis: if you are HLAB27 negative, you are much less likely to have a diagnosis...
POTS are diagnosed by a tilt table test, not a blood biomarker!
The finding of auto antibodies enlights on the pathologic process at play, which is a great finding anyway.

I hope some treatment for auto-immunity will ensue with success.
 

Gingergrrl

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Thank you so much for posting this study @Belbyr and I had not seen it before. It really has a lot of credibility and Dr. Blair Grubbs is one of the top POTS specialists in the world.

"Researchers screened the patients' blood for autoantibodies against nine receptors. A handful of patients showed elevated levels against all nine. But it was the prevalence of adrenergic A1 subtype receptor autoantibodies that make their findings so intriguing.
I was going to copy this quote from the article but you beat me to it, Patti! When they said that the patients blood was screened for nine autoantibodies against receptors, do you or Belbyr know if they used the Cell Trend Panel from Germany or another lab?

I was positive for seven out of nine autoantibodies in early 2016 on the Cell Trend Panel (done twice to be sure) and then after IVIG and Rituximab, I re-did the panel in 2018 and I was only positive for four of the seven. However, one of the four that remained positive even after treatment was the a1-adrenergic autoantibody like in this study (and the majority of symptoms that remain for me are POTS related). But unlike the people in the study, I have other autoimmune diseases besides POTS.

"I think that we have identified a biomarker. We now might have the ability to diagnosis this, or at least have an inkling. Like other autoimmune disease, we can take a blood sample and detect if there are increased levels of autoantibodies present. According to our results, autoantibodies against this particular receptor should be present in about 90 percent of patients with POTS,"
I believe that some day it will be shown not only that there is an autoimmune sub-set of POTS but that POTS itself is an autoimmune disease (like this study presents). Perhaps the 10% of people who test negative for the alpha-1 adrenergic autoantibody are sero-negative (like in other illnesses, there is often a sero-negative group).

My daughter's anti alpha-1-adrenergic antibodies are almost 16 (with greater than 7.0 being positive).
@Sad Dad Was your daughter tested through Cell Trend in Germany or another lab? My a-1 adrenergic autoantibodies were always in the 20's. We did the test 3x total and they were 27, 22, and 29.

But, if these antibodies are so rampant in POTS & many CFS patients, why did the Rituximab CFS trials fail? Rituximab should have knocked out those bad antibodies, correct?
My personal opinion is that the alpha and beta adrenergic autoantibodies reflect POTS and not ME/CFS. I think if a trial had been done in patients with POTS with these autoantibodies, it would be very different than a trial of people with ME/CFS who may or may not have POTS and/or autoimmunity.

I don't know why some autoimmune diseases fail in Rituximab trials, but it happens.
I have written to an insane length in other threads re: my opinion of why the Fluge and Mella Ritux trial did not succeed so I don't want to take this thread off track.

But even in these diseases, there was anecdotal reports of rituximab success which is very confusing.
Absolutely, there were individual responders.

I guess that reminds me of rituximab failing in lupus trials
Even in RA (which Ritux is FDA approved to treat), there are non-responders.
 

pattismith

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I'm glad you came to give your opinion here Ginger, you are the specialist!
My personal opinion is that the alpha and beta adrenergic autoantibodies reflect POTS and not ME/CFS. I think if a trial had been done in patients with POTS with these autoantibodies, it would be very different than a trial of people with ME/CFS who may or may not have POTS and/or autoimmunity.
.
it may be different, but at least ME/CFS patients should have reported some improvement with their POTS?
I guess they didn't test it Before/After, a pity they don't...
 
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I do not think this research applies to most of us. POTS can occur on its own, you dont need to have ME to have POTS. Since autoimmune drugs have failed to make a difference in ME, it is likely that the POTS in ME occurs trough a different mechanism than the stand-alone POTS.

I would speculate that the POTS in ME is more of an upstream problem, i.e. brain sending the wrong signals, while the stand-alone POTS is a downstream one, i.e. nerves not functioning properly.
 

Belbyr

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Yeah he used cell trend panels, which I was negative on even though I clearly have POTS. I heard there was a batch of tests they did and everyone was negative from that batch, myself included.

When I saw Dr Klimas she said 90%+ of her CFS patients have POTS and I was the first negative cell trend they have seen!
 

Gingergrrl

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it may be different, but at least ME/CFS patients should have reported some improvement with their POTS?
I think there are some ME/CFS patients who do not have POTS, or they may have a mechanism that for all intent and purposes is the same but is not Autoimmune POTS. I cannot wait for the day until the science is really well understood re: POTS and the different sub-types and causes.

Yes, those were Cell Trends results.
Thx for confirming. Did your daughter do any treatments for autoimmunity or was she positive for any autoantibodies outside of the Cell Trend Panel?

Yeah he used cell trend panels
Thank you so much for confirming this @Belbyr (re: Dr. Grubbs team at Toledo using the Cell Trend Panel for his study). I am so glad that this panel is being taken seriously now.

When I saw Dr Klimas she said 90%+ of her CFS patients have POTS and I was the first negative cell trend they have seen!
That is so interesting. How did she (or you) interpret that?

I even failed that since I got my period during the test and nobody said that invalidaste. Second one was positive after suffering for 2 years.
Why would someone having their period invalidate the results of a Tilt Table Test? (I apologize if the answer is obvious :))
 

Gingergrrl

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I had a few 'at risks' on the test but nothing in the 'positive' range. Apparently other POTS patients are testing negative too. I wonder what's up?
The only thing I can think of is either that there is a group of patient with POTS who do not have "Autoimmune POTS" or they are sero-negative to the autoantibodies (like in many other illnesses).
 

Belbyr

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I'm going to try the Mayo Dysautonomia Autoimmune Panel and see If I have one of those. I'm trying to think of every kind of cause... I don't think I have EDS and I've been tested for all the major autoimmune disorders. I did see where Dr. Goodman said that 40-70% of Sjogrens AAB's are false negative when a lip biopsy is done. I might need one of those.
 

Gingergrrl

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I'm going to try the Mayo Dysautonomia Autoimmune Panel and see If I have one of those. I'm trying to think of every kind of cause...
The Mayo DYS1 Panel is really solid and will give you good information. I tested positive for (the same) two autoantibodies on the PAVAL and DYS1 panels from Mayo and it was probably the single most helpful test of everything that I have done (as far as insurance and treatment). We knew I had severe Dysautonomia but this proved that it was autoimmune mediated (in addition to the Cell Trend Panel, positive ANA, having Hashimoto's Disease, and other autoimmune markers).