Study: Animal models of POTS created, then treated

[Belbyr]

https://www.ahajournals.org/doi/10.1161/JAHA.119.014084

 

[pattismith]

Adrenergic Autoantibody‐Induced Postural Tachycardia Syndrome in Rabbits

Hongliang li

Abstract

Background

Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits.
Methods and Results

Eight New Zealand white rabbits were coimmunized with peptides from the α1‐adrenergic receptor and β1‐adrenergic receptor (β1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope‐mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the β‐adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of β1AR antibodies. In contrast, the blood pressure response to infusion of the α1‐adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1‐adrenergic receptor antibodies. Injections of antibody‐neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays.
Conclusions

The differential allosteric effect of α1‐adrenergic receptor and β1ARautoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac β1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.

 

[Gingergrrl]

These data support evidence for an autoimmune basis for postural tachycardia syndrome.

This was an excellent article and I read it a few days ago and wanted to post it but did not have a chance. Thank you for posting it Belbyr & Patti. I think the evidence that supports an Autoimmune basis of POTS (either as a subgroup of POTS or of all POTS) is becoming indisputable.

 

[pattismith]

These recent findings are raising several questions...

. POTS are more prevalent in hypermobile people , could it be that have some immune problem that can explain that ?

. POTS exists in people with brainstem compression and can resolve after fusion, so I wonder if it's auto-immune in that case

 

[bread.]

This was an excellent article and I read it a few days ago and wanted to post it but did not have a chance. Thank you for posting it Belbyr & Patti. I think the evidence that supports an Autoimmune basis of POTS (either as a subgroup of POTS or of all POTS) is becoming indisputable.

definitely a subtype, maybe a big one, but 100% definitely a subtype.

These recent findings are raising several questions...

. POTS are more prevalent in hypermobile people , could it be that have some immune problem that can explain that?

I think there is a connection to the immune system, seems obvious at this point. It could be as simple as bodywide tissue issues due to collagen misfolding that the immune system reacts to naturally (leaky gut for example, but also mast cell issues)

 

[Belbyr]

definitely a subtype, maybe a big one, but 100% definitely a subtype.

I think there is a connection to the immune system, seems obvious at this point. It could be as simple as bodywide tissue issues due to collagen misfolding that the immune system reacts to naturally (leaky gut for example, but also mast cell issues)

Yeah there was about 10% that were negative. I was negative on that test too.

 

[Gingergrrl]

definitely a subtype, maybe a big one, but 100% definitely a subtype.

I agree that it will end up being a big subgroup but will probably not be 100% (and so much about POTS is still unknown). But it is thrilling to see the increased research and interest in POTS.

I think there is a connection to the immune system, seems obvious at this point. It could be as simple as bodywide tissue issues due to collagen misfolding that the immune system reacts to naturally (leaky gut for example, but also mast cell issues)

I also agree that it has to be immune-mediated. I developed POTS literally immediately after having a viral infection (in Jan 2013) and remember the exact date of the first episode. Then later all of the viral stuff shifted into autoimmunity (in my case).

Also, I belong to a FB group for people with calcium channel autoantibodies and almost every single person also has POTS (and we do not know why but the only connection seems to be autoimmunity). Plus the number of people who have both POTS and MCAS (in general) is staggering.

Yeah there was about 10% that were negative. I was negative on that test too.

I think it may turn out that there are other autoantibodies that correlate with POTS in addition to those on the Cell Trend Panels.

 

[Belbyr]

Interesting on the calcium channel antibodies. I see they are on the DYS2 and GID2 Mayo Clinic autoimmune panels.

I called and they said a doctor has to order the test, I see my doctor Thursday and have their print outs for him. I saw a Dr Abell and a Dr Laura Pace mention them in a speech about gastro motility disorders. Apparently just about everyone with motility issues has signs on 1 of the following on their full thickness stomach biopsies (after diabetes has been ruled out):
1. mast cells 2. eosinophils 3. lymphocytes 4. tryptase