Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Protein-Coupled Receptor Autoantibodies (Gunning et al., 2021)

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Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Protein-Coupled Receptor Autoantibodies (Published: 6 February 2021 )

Abstract

A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients (n = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. Patients with autoimmune disorders have been reported with a variety of elevated cytokines and cytokines (such as rheumatoid arthritis); thus, we evaluated a limited number of cytokines/chemokines in POTS patients with elevated adrenergic and muscarinic receptor autoantibodies.

We utilized the plasma of 34 patients from a previous study; all of the patients (100%) had autoantibodies against the A1 adrenergic receptor and 55.9% (19/34) had autoantibodies against the M4 muscarinic acetylcholine receptor. In particular, the plasma cytokine/chemokine levels were measured as biomarkers of inflammation by Quantibody® technology (Raybiotech, Peachtree Corners, GA, USA). We also evaluated the platelet dense granule numbers, as these patients frequently complain of symptoms related to platelet dysfunction. Patients were predominantly young females who displayed a multitude of co-morbidities but generally reported viral-like symptoms preceding episodes of syncope.

Eighty five percent (29/34) had platelet storage pool deficiency. Patients had elevations in five of ten cytokine/chemokines biomarkers (IL1β, IL21, TNFα, INFγ, and CD30), whereas two biomarkers had decreased levels (CD40L and RANTES). Our observations demonstrate that POTS patients known to have autoantibodies against the G-protein-coupled adrenergic A1 receptor have abnormal plasma concentrations of inflammatory cytokines.
 

Learner1

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High on CellTrend adrenergic A1 and M4.
Cytokines were:
Screenshot_20210227-212340.png


My tests highly suggested autoimmune processes going in, so, this is why, I chose to go the autoummunity direction of treatment, Rituximab, and high dose IVIG for treatment., Working with the viruses through antivirals and infections with appropriate antibiotics were also critical.

Hope this helps!
 

SlamDancin

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I have high cell trend AABs towards a1 and a2. Antagonists to these receptors, for example Trazodone for a1 and Yohimbine for a2, make me very sick. Antagonizing a1 gives me syncope and antagonizing a2 gives me bad tachycardia. Both are their own brands of hell. I’ve repeated this with different ligands over time so it appears to reflect that the celltrend results are accurate and these AABs are agonistic as reported in some papers and may be a compensatory measure. Unfortunately a1/a2 agonists haven’t been super helpful.
 

Learner1

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I have high cell trend AABs towards a1 and a2. Antagonists to these receptors, for example Trazodone for a1 and Yohimbine for a2, make me very sick. Antagonizing a1 gives me syncope and antagonizing a2 gives me bad tachycardia. Both are their own brands of hell. I’ve repeated this with different ligands over time so it appears to reflect that the celltrend results are accurate and these AABs are agonistic as reported in some papers and may be a compensatory measure. Unfortunately a1/a2 agonists haven’t been super helpful.
It is not clear to me whether one wants agonists or antagonists if one has adrenergic or muscarinic antibodies. How are you deciding you need antagonists?
 

SlamDancin

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@Learner1 It wasn’t clear to me either so I just went ahead and tested both ways. I take Butcher’s Broom right now for alpha adrenergic/muscarinic agonism and it seems to help some. I have OI but not full POTS. I will try to find some references but there is evidence that these type of AAB’s might be a compensatory function of the immune system that you do not want to interfere with.
 

Learner1

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These give an interesting tutorial on how the autonomic nervous system and adrenergic and muscarinic receptors work:




I'm just not sure how the antibodies interact and I'd like to more about your compensatory theory. My doctor thinks my chronic infections triggered the antibodies and I'm immunodeficient as well as having 2 other kinds of autoimmunity.

IVIG, beta blockers and Huperzine A have helped, and Rituximab wiped out most of my symptoms excepting high BP, so I still need the beta blocker.