Autoimmune Basis for Postural Tachycardia Syndrome

[Firestormm]

Via Tate Mitchel and Co-cure

26 February 2014
Autoimmune Basis for Postural Tachycardia Syndrome

Hongliang Li, MD, PhD;Xichun Yu, MD;Campbell Liles, BS;Muneer Khan, MD; Megan Vanderlinde‐Wood, MD;Allison Galloway, MD;Caitlin Zillner, BS;Alexandria Benbrook, BS; Sean Reim, BS;Daniel Collier, BS;Michael A. Hill, PhD;Satish R. Raj, MD;Luis E. Okamoto, MD; Madeleine W. Cunningham, PhD;Christopher E. Aston, PhD;David C. Kem, MD

Background
Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR).

Methods and Results
Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for α1AR autoantibody‐mediated contractility using a perfused rat cremaster arteriole assay.

A receptor‐transfected cell‐based assay was used to detect the presence of β1AR and β2AR autoantibodies. Data were normalized and expressed as a percentage of baseline.

The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69±3% compared to 91±1% of baseline for healthy controls, P<0.001) when coexisting β2AR dilative activity was blocked; and this was suppressed by α1AR blockade with prazosin.

POTS sera acted as a partial α1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased β1AR activation (130±3% of baseline, P<0.01) and a subset had increased β2AR activity versus healthy subjects.

POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced β1AR and β2AR agonist activity. Autoantibody‐positive POTS sera demonstrated specific binding to β1AR, β2AR, and α1AR in transfected cells.

Conclusions
POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR‐mediated tachycardia.

Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.

New evidence of autoimmunity in POTS!
February 25, 2014 autoimmune, POTS, research

IS POTS AN AUTOIMMUNE DISEASE?

Big news this week in POTS research! Researchers from the University of Oklahoma and Vanderbilt University have identified evidence of adrenergic receptor autoantibodies in a small group of POTS patients, suggesting that POTS may be an autoimmune condition in these patients. The study was published in the Journal of the American Heart Association (JAHA). JAHA is an official journal of the American Heart Association, so this is great news for POTS awareness!

To help patients better understand what this means, Dr. David Kem from the University of Oklahoma Health Sciences Center has kindly provided Dysautonomia International with a patient friendly explanation of this complex research. Before we get to Dr. Kem’s explanation, let’s go over the basics of adrenergic receptors and autoantibodies...

Read blog...

@Legendrew thought you might be interested as well as others.

 

[Kate_UK]

What did Alan and Kathleen Light find about adrenergic receptors, is it similar to this, or something different?

 

[Firestormm]

What did Alan and Kathleen Light find about adrenergic receptors, is it similar to this, or something different?

I can't remember. The above is a small study but hopefully they will repeat it with more patients (and controls) if they can secure funding. Personally I don't tend to follow research in this area very closely but thought it might be of interest to those affected by POTS. I couldn't understand the paper but thought the blog was easier to follow.

 

[Legendrew]

Interesting stuff, the sudden onset triggered by infections and female predominance has always suggested such, and now we have a glimpse as to what exactly is 'going on' in POTS. I look forward to a larger study which it sounds they are already planning.

 

[Ema]

I was reading about some "new" autoimmune antibodies that Vandy researchers were looking for just a few weeks ago. I looked for the "further research" they alluded to, but couldn't find anything.

Must have been just *this* much too early. LOL.

Thanks for posting!

 

[Valentijn]

What did Alan and Kathleen Light find about adrenergic receptors, is it similar to this, or something different?

That was adrenergic alpha-2A, so a bit different from receptors for adrenergic alpha-1A or adrenergic beta. But they are all involved in various aspects of the same system, so it might go toward explaining why some people have POTS, some have NMH, some have both, and some have hypertensive POTS.

 

[adreno]

This fits my experience. Alpha-1 agonism seems to abolish OI for me, but I still have tachycardia. Beta-blockers take care of tachycardia, but makes OI worse. Perhaps combining alpha-1 agonism (or alpha-2 antagonism) with a beta blocker would perhaps be optimal.

Is there any way to clear the antibodies? Would an antiviral help?

 

[Bob]

Does anyone happen to know if these auto-antibodies were previously known to science? i.e. had they previously been detected in other research? (I haven't read the full paper.)

 

[Marco]

From the above :

POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced β1AR and β2AR agonist activity. Autoantibody‐positive POTS sera demonstrated specific binding to β1AR, β2AR, and α1AR in transfected cells.

A while back I wrote about a condition called complex regional pain syndrome - a chronic multi-symptom disorder that follows a relatively trivial peripheral injury with symptoms as follows :

Most intriguing are the systemic co-morbid symptoms that seem not only disproportionate to the initial injury, but at first glance seem completely unrelated and difficult to explain.

These include widespread hyperesthesia and allodynia, deep bone and joint pain, increased levels of pro-inflammatory cytokines suggesting systemic low grade inflammation, cardiac symptoms (chest pain spreading to the arm, neck and jaw, syncope, POTS, and increased heart rate and reduced heart rate variability reflecting generalized autonomic dysfunction) and gastrointestinal (including gastroparesis and reflux) and urological symptoms.

An autoimmune contribution to CRPS now seems likely with similar receptors affected :

An autoimmune contribution to CRPS now appears likely given recent findings that 90% of an adult CRPS cohort had autoantibodies (agonistic, therefore upregulating) to either the beta(2)-adrenergic receptor (β2AR) or the muscarinic acetylcholine receptor (M2R). Fifty percent of the cohort had autoantibodies to both. 10

“The key concept here is that the development of autoimmunity to specific neuroautoantigens may be the initiating event for many cases of CRPS. Psychological stressors, physical trauma, infectious agents, and/or genetic susceptibility could all play a role in the breakdown of self-tolerance, and the onset of an autoimmune response. This set of etiological linkages fits well with documented clinical experience with CRPS (Mitchell 1872; Birklein et al. 2000). Psychological stressors and immunologic priming have been linked to the enhanced activation of microglia to nervous system injury (Frank et al. 2007; Hains et al. 2010).”

I thought CRPS might be quite a good model for ME/CFS :

http://www.cortjohnson.org/blog/201...lgia-mecfs-spreading-neuroinflammation-model/

 

[kangaSue]

POTS is a symptom that features in this recent review article on autoimmune diseases.
http://www.hindawi.com/journals/ad/2013/549465/

 

[taniaaust1]

. Personally I don't tend to follow research in this area very closely but thought it might be of interest to those affected by POTS. I couldn't understand the paper but thought the blog was easier to follow.

Thank you very much for that

 

[taniaaust1]

It would be interesting if something like POTS research leads ME to be finally known to all as an autoimmune disease. I have the POTS due to the ME.

 

[est_sunshine]

I've got Pots and I recently checked if I had the SLC6a2 snp using 23 and me and livewello and I don't. So.... Am thinking if it's not a genetic issue with the NE transporters it could be antibody driven. I hope they get some answers from the next larger study. Earlier this year they used the Dysautonomia conference in the US to collect blood from pots patients I hope this sample shows a link and treatment options follow soon

 

[est_sunshine]

Am thinking of trying Anatabine supplement which has been shown to help reduce thyroid antibodies

 

[Gingergrrl]

@Firestormm

My brain can't follow anything scientific today but thank you for posting this study and tachycardia was the very first symptom that I got following mono before I had full-blown dysautonomia and ME/CFS.

My 2nd cardiologist said she had seen inappropriate sinus tachy/POTS in female patients around my age (then 42) who had mono/EBV in the prior year. This was the first time I made any connection. She had no idea how to treat it other than trying beta blockers and hoped it would resolve on it's own in six months (which it didn't.)

I am now on a whole cocktail of meds for cardiac/autonomic issues but nothing is working correctly at the moment which is very discouraging.

 

[est_sunshine]

There are currently treatments like IVIG and plasmapheresis that will reduce the antibodies but I don't think they are permanent. I'm sure now they are looking in the right place solutions will come.

 

[kisekishiawase]

Is this antibody not limitted of effecting pots patient only? From googling i also find other heart issue.
Why does it say betablocker wont work

Anyway it seems its not known to many doctors.
Im worried also what to do then.

 

[kisekishiawase]

Is this the same?
BBC News | Health | Immune system 'causes heart failure
http://news.bbc.co.uk/2/hi/health/274921.stm
http://www.sciencedaily.com/releases/1999/02/990209072908.htm
http://www.sciencedirect.com/science/article/pii/S1568997214001657

Its published on 1999 though.
Sounds bad
But it seems its still vague and no test, treatment available.
Also it says bad things about beta blocker which worries me

 

[SDSue]

Has this already been posted? Dr. David Kem of OU interviewed on Oklahoma News 9:

The OU researchers have "identified a decoy protein to short-circuit those antibodies responsible for the condition”.

Dr. Kem: “This would be a cure, and we hope even an oral cure."

http://www.news9.com/clip/11462578/medical-minute-pots

 

[Sushi]

This is a really short clip and worth watching. There is always the question, when you talk about a cure, what are you curing, what caused this? This is talking about a sort of by-pass, or as they say short-circuit--which would be very welcome, but what went wrong that might still need to be fixed after the "short-circuit" treatment?

Sushi