Autoimmune Pots Cases Are Popping Up On Pubmed

[Relax86]

I have recently had a positive ANA, false for scleraderma, negative for sjogrens, positive for low complement (C3 I think). In the beginning of this pots flare - jan 2012 I was prescribed hydrocortisone for a diagnosis of Adrenal fatigue and I responded very well to it. I went on and off HC a few times in the year as a few Doc's felt it was going to destroy my adrenals. I generally took about 10-15mg per day and it always helped. So my current rheumatologist says based on my current blood tests it's no wonder I felt better on the HC. She doesn't exactly know what's wrong but at least she's willing to test, look and not peg me for a nutcase. I may, however, turn her on to this thread.

[ramakentesh]

Mayo think most pots is autoimmune and with good reason although autoantibodies evidence has not been hugely compelling yet.

that's close but dr kem did a more recent study. On phone so can't post.

[issie]

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[ramakentesh]

I hear a few POTSies have done ok on LDN - some improvement but not a massive amount. Worth trying though.

http://edrv.endojournals.org/cgi/content/meeting_abstract/33/03_MeetingAbstracts/OR48-1

Autonomic Autoantibodies with Allosteric Activity in Idiopathic Postural Orthostatic Hypotension (IOH) and Tachycardia Syndrome (POTS): A New Mechanism Hongliang Li, MD, PhD¹, Muneer A Khan, MD¹, Megan D Vanderlinde-Wood, MD¹, Allison L Galloway, DO¹, Caitlin M Zillner, BS¹, Xichun Yu, MD¹ and David C Kem, MD¹

¹ Medicine, University of Oklahoma and Veterans Adminstration Medical Centers Oklahoma City, OK

Objective: Patents with postural orthostatic tachycardia syndrome (POTS) have a variable drop in BP that is partially or completely compensated by the exaggerated tachycardia. We have reported circulating agonistic autoantibodies to the β2 adrenergic receptor (β2AR) and M3 muscarinic receptor (M3R) serve as vasodilators and cause or exacerbate orthostatic hypotension. Autoantibodies to the β1 adrenergic receptor (β1AR), M2 muscarinic receptor (M2R) and α1 adrenergic receptor (α1AR) are variably co-present and may explain the pathophysiology of this complex syndrome.Methods: Patients were categorized into 16 with idiopathic orthostatic hypotension (IOH), 7 with POTS and 10 normal control subjects. Purified IgG from all patients and healthy control subjects were examined in a receptor-transfected cell-based assay for β1AR and β2AR activation, and a β-arrestin-based assay for M3R activation. Data are expressed as % of baseline (Mean ± SD). All subjects gave informed consent.Results: Patients with IOH and POTS had increased β2AR activity (122 ± 14% and 121 ± 12%) compared to normal subjects (106 ± 8%, P=0.007). β1AR activity was similarly increased in both IOH and POTS compared to normal controls. By contrast, M3R activation in IOH was increased (141 ± 32%) over normal controls (99.4 ± 12 %, P=0.002) while activity for POTS M3R was not significantly increased (114 ± 30%). IOH and POTS had similar M2R inhibition of forskolin-induced cAMP production (72 ± 16% and 76 ± 12%) compared to normal controls (97 ± 4%). We have demonstrated the vasodilatory capacity of the β2AR and M3R autoantibodies in vitro using isolated perfused rat cremaster arterioles. Several subjects had increased ELISA evidence for autoantibodies to α1AR.Discussion: Vasodilatory autoantibodies to β2AR and M3R are present in IOH patients suggesting these autoantibodies cause or exacerbate orthostasis by altering the compensatory postural vascular response. Patients with POTS also demonstrate a high proportion of activating autoantibodies and may represent a subset with autoantibodies to the α1AR that are partially inhibitory to the native norepinephrine ligand in vivo.Conclusion: These data support the concept that circulating agonistic autoantibodies are present and active in IOH and in POTS. POTS may represent one end of a spectrum of autoimmune disease with the potential for autoimmune allosteric inhibition of norepinephrine action in α1AR but not in β1/2AR.

[ramakentesh]

In the old days they just sucked out a patients blood and stuck it in a rabbit and watched if it got sick...

[sue1234]

So, from this, are there any tests out there that we patients can have run to test for these autoantibodies? Or, is everything still in a research phase?

Patience is not a virtue for me.

[ramakentesh]

Unfortunately not. And sometimes when autoantibodies are found they dont activate what they are supposed to activate and are just an artifact.

But anyway - the three studies - firstly the A3 acetylcholine receptor antibodies in 14% of POTS, the second study that found a large spread of circulating autoantibodies against a variety of cardiac proteins including one that knock-out mice models without the protein looked almost kinda POTSie, and the last article on Beta 1 and 2 receptor autoantibodies combined with competitive antibodies that block a1 receptors are all interesting.

[Zap]

This thread is of major interest to me, given my response to dexamethasone. I recently had a bunch of tests done by my new autonomic neuro. She has a decorated history and is definitely on top of research AND thinks that POTS is just a part of the bigger picture.

My recent tests have some things finally starting to fall out-of-range. I consider that a start. I've suspected for a while that autoantibodies to the alpha/beta receptors could definitely be at play. Inquired with Vanderbilt once I read somewhere that they found them - but they weren't aware of any test panels.

This is definitely interesting and the research to keep a watch on.