Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome (2018) Yu et al

Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome

Authors:Xichun Yu, Hongliang Li, Taylor A. Murphy, Zachary Nuss, Jonathan Liles, Campbell Liles, Christopher E. Aston, Satish R. Raj, Artur Fedorowski, David C. Kem
(from Oklahoma, Sweden and Calgary)

Abstract

Background:
Both the adrenergic and renin‐angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1‐adrenergic and β1/2‐adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS.

Methods and Results:
Serum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1‐adrenergic receptor.

Conclusions:
Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS

Clinical Perspective
What Is New?

-Activating autoantibodies to the posture‐related angiotensin II type 1 receptor were present in a cohort with postural orthostatic tachycardia syndrome.

-Angiotensin II type 1 receptor–activating autoantibodies had a negative allosteric effect on angiotensin II action.

• What Are the Clinical Implications?
  • These data support previous reports for an impaired responsiveness to angiotensin II in postural orthostatic tachycardia syndrome and a rationale for the beneficial impact of salt loading on blood pressure and pulse responsiveness in postural orthostatic tachycardia syndrome.
    
    
  • Pharmacological or physiological suppression of relevant autoantibodies may have a therapeutic benefit in postural orthostatic tachycardia syndrome

Link to paper (open access) : http://jaha.ahajournals.org/content/7/8/e008351

 

As an aside note, I wasn’t sure where to put this paper. While this is not ME research, POTS is a very significant comorbidity which in my opinion deserves being posted alongside with ME related research. This is an important paper.

 

Where do these shitty antibodies come from? And why?

 

Auto-immunity is still a scientific mystery, but psychiatrists and psychologizers would say ‘child abuse’.
In this case with this paper, we have a potential to better treatments for POTS, however this is a small sample size. I wonder if a commercial test will follow.

 

Here is an interesting bit:

(Bolding mine)

 

Immunoglobulin?

 

@Gingergrrl you have some experience with POTS, antobodies and immunoglobulin?

 

No, they mentioned Losartan. Angiotensin 1receptor blockers.

 

I think you meant "autoantibodies" (autoimmunity) and if so, then yes, I have experience with POTS, many different autoantibodies, high dose IVIG, and also Rituximab. I have a very long thread about it all on the other board (it's close to 40 pages now but goes off topic several times... and then back on track)!

I am happy to answer any questions re: my personal experience if it would be helpful. I am very interested in testing for the autoantibody in this study (Angiotensin II Type 1 Receptor) through Cell Trend in Germany but I have not done it yet. My doctor is open to me trying Losartan regardless (if I wanted to) but since Atenolol works well for me for POTS, I would not want to make any changes right now unless I had confirmation of the AT1R auto-antibody first. I'll be discussing it with my doctor further in my next phone consult in a couple weeks.

 

There is now a commercial test for this autoantibody through Cell Trend in Germany. To my knowledge you cannot test for this autoantibody in the United States.

IVIG is now being used by many doctors for POTS in cases like mine in which they suspect the patient has Autoimmune POTS vs. another sub-type.

The treatment that is being mentioned for this new AT1R autoantibody is Losartan. If I have this autoantibody, I am open to trying it as I mentioned above but would not try it at present without this confirmation.