New Paper: Autoimmunity in POTS.

[Remy]

Europace. 2016 Oct 4. pii: euw154. [Epub ahead of print]
Antiadrenergic autoimmunity in postural tachycardia syndrome.

Fedorowski A1, Li H2, Yu X2, Koelsch KA3, Harris VM3, Liles C2, Murphy TA2, Quadri SM3, Scofield RH3, Sutton R4, Melander O5, Kem DC2.
Author information


Abstract

AIMS:

Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR).
METHODS AND RESULTS:

Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro.

Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.
CONCLUSION:

These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.
KEYWORDS:

Adrenergic receptors; Allosteric activation; Autoimmunity; Postural tachycardia syndrome; Vasovagal syncope

 

[weyland]

This paper, and Kem's previous one, finally convinced me to get tested for these autoantibodies. Their evidence is pretty convincing, and makes a heck of a lot of sense if it is true.

 

[Remy]

This paper, and Kem's previous one, finally convinced me to get tested for these autoantibodies. Their evidence is pretty convincing, and makes a heck of a lot of sense if it is true.

Where are you getting tested?

 

[weyland]

Celltrend in Germany. I don't believe these are available commercially anywhere else yet.

 

[Remy]

Celltrend in Germany. I don't believe these are available commercially anywhere else yet.

I was just looking at the lab requisition form for Celltrend. It's all a bit overwhelming!

I'm thinking about doing it too, but of course it's a bit of a financial commitment, given the price.

I wonder if it would really change my treatment to test positive at this point since I'm already doing Hizentra (subQ IVIG).

Please share your results, if you do it! I'm super curious...

 

[weyland]

I'd probably avoid doing any antibody testing while receiving immunoglobulins.

Please share your results, if you do it! I'm super curious...

Will do. I'm really curious as well. I'm becoming interested (i.e. desperate) in the idea of trying interferon alpha, but if my POTS is autoimmune and it might worsen that then I will need to consider it carefully.

 

[Remy]

What’s new?
† Serum from patients diagnosed with postural tachycardia syndrome contains circulating autoantibodies with a direct stimulatory effect on adrenergic receptors.
† The autoantibodies may also exert an allosterically mediated positive modulatory effect upon b1AR and a negative modu- latory effect on a1AR activity.
† These and possibly other yet-to-be identified immunoglobu- lins with different target epitopes might explain different constellations of symptoms in POTS.
† This concept, if validated, would provide concrete support for novel therapeutic approaches against POTS based on immunotherapy.

I have the full paper now. PM me if you'd like to read it!

 

[SarahTee]

Dr Fedorowski talking about some more research done since:

 

[SarahTee]