Autoimmunity has become a huge issue in POTS (postural orthostatic tachycardia syndrome) and is becoming a major one in chronic fatigue syndrome (ME/CFS). The autoimmunity revolution underway in POTS – few now believe the disease doesn’t have a major autoimmune component – has come fast and fierce. Although it was less than five years ago that autoimmunity began to be a serious topic in POTS, researchers are now suggesting that the autoimmune findings in POTS may be the tip of the iceberg. They believe their results may play a role in other autonomic disorders including ME/CFS.
The fact that this is happening in POTS – a condition which has received little funding from the NIH – is encouraging. It shows that even diseases without much funding can still at times make rapid strides if researchers explore the right areas.
The Autoimmunity Revolution in POTS (Postural Orthostatic Tachycardia Syndrome)
Dr. Kem has been behind a growing revolution in how to think about POTS. He believes that EBV, Lyme disease and other infections have activated enzymes that clip off loops found on the alpha/beta adrenergic receptors. He believes the damage to those receptors has so tweaked the immune system that it’s begun attacking them – triggering an autoimmune response.
This work goes back almost twenty years to a finding that α1AR autoantibodies can attack a second extracellular loop (ECL2) in the adrenergic receptors found on our blood vessels.
Autoimmunity findings are redefining how we think of POTS.
Jump forward to to 2011 when Kem and other researchers at the University of Oklahoma found autoantibodies to adrenergic and muscarinic receptors in a small cohort of patients (n=6) whose blood pressure falls dramatically upon standing (orthostatic hypotension). Most of these patients were medical mysteries – until this study; a larger, but still small study (n=20) in 2012 duplicated their findings and suggested that autoimmunity might be playing a role in other diseases characterized by problems with standing.
Then, in 2014, the Oklahoma team also found β1AR‐activating autoantibodies in all of the POTS patients it studied and β2AR-activating autoantibodies in some. At this point, the Oklahoma team suggested that POTS may very well be an autoimmune disease and laid out a model of POTS pathophysiology.
“These data support the addition of POTS to a growing number of cardiovascular entities with an autoimmune pathophysiology.” Li et. al.
This damaged adrenergic receptor made it more difficult for norepinephrine (NE) to trigger a vasoconstrictor response to standing, leaving POTS patients needing 55% more NE than normal to tighten down their blood vessels. The “catecholamine surge” that resulted was a compensatory mechanism used to override the adrenergic receptor malfunction. The increased levels of stress hormones needed to compensate would likely leave POTS patients “wired and tired”.
The problems POTS patients had maintaining their blood pressure caused their baroreceptors to become twitchy and hypersensitive. The end result of all this was the tachycardia (rapid heart beat) seen in POTS. It was clear that neither blood pressure nor heart rate regulation were working properly in POTS and the researchers’ autoantibody findings could explain why. They stated that:
“These contrasting effects provide an appealing explanation for the cardiovascular effects associated with upright posture in those so afflicted.”
Nor did they believe their findings were only going to apply to POTS. They believed a range of autoantibodies were likely producing a spectrum of cardiovascular dysautonomias. The kind of dysautonomia you had depended on the types and levels of autoantibodies present. The autoantibodies typically didn’t turn off a receptor response; instead, in an allosteric fashion, they inhibited its functioning to various degrees. They proposed that a novel therapeutic using IVIG or “decoy peptides” could be the answer for many with POTS and related diseases.
The autoantibody work in POTS was just beginning, however. In a 2017 paper, the authors stated they believed the autoantibodies they’d identified were only in part responsible “for many of the cardiovascular manifestations” they’d seen in POTS patients. They believed that other autoantibodies were also playing a role, and in a 2018 paper in the Journal of the American Heart Association, they showed that as well.
Another Damaged System
Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome
Xichun Yu, MD, 1 , † Hongliang Li, MD, PhD, 1 Taylor A. Murphy, BS, 1 Zachary Nuss, BS, 1 Jonathan Liles, BS, 1Campbell Liles, BS, 1 Christopher E. Aston, PhD, 2 Satish R. Raj, MD, 3 , 4 Artur Fedorowski, MD, PhD, 5 , 6 , † andDavid C. Kem, MD. J Am Heart Assoc. 2018 Apr 17; 7(8): e008351. Published online 2018 Apr 4. doi: 10.1161/JAHA.117.008351
It turned out that another system that helps us stand is damaged in POTS as well. The renin-angiotensin-aldosterone system helps regulate our blood pressure when we stand, and its receptor – the angiotensin II (Ang II) type I receptor (AT1R) belongs to the same family as the adrenergic receptors the Oklahoma team had found problems with. That suggested to them that these autoantibodies might also be present in POTS patients.
Autoantibodies affecting the renin-aldosterone-angiotension system which regulates blood pressure were also found in POTS.
They were right. While none of the controls or the disease control group (vasovagal syncope) had autoantibodies to the angiotensin receptor, most of the 23 POTS patients in the study did. Further study revealed that the autoantibodies were indeed interfering with the system’s functioning.
The renin-angiotensin-aldosterone system kicks in during more prolonged standing, but an animal model indicated that the effects were mostly the same as the earlier results in POTS – an inability to properly squeeze the blood vessels and stop the blood from pooling in the lower body. The end result was lower blood pressure levels in POTS patients with the ATIR antibodies than in POTS patients without them.
The authors believed that the new autoantibodies may explain a mysterious group of POTS patients who have elevated angiotensin II levels but low aldosterone levels. They also suggested that the salt loading POTS patients typically do may be an attempt to compensate for this receptor’s blockage.
In his conference talk, Kem reported that the M2 receptor in POTS patients is resistant to acetylcholine, the neurotransmitter driving the vagus nerve and the parasympathetic nervous system. Studies indicate that the M2 receptor blockage found results in a vagal withdrawal (reduced vagus nerve activity). Because the vagus nerve regulates the sympathetic nervous system, which helps control the heart rate, vagal withdrawal is yet another way to produce the heart rate increases seen in POTS. (Vagal withdrawal in POTS, ME/CFS and FM is reflected in low heart rate variability results).
By 2018, then, the University of Oklahoma group had demonstrated, in mostly small studies, the presence of four different autoantibodies (α1AR, β1/2AR) that affect cardiovascular functioning in POTS. Earlier, the same research group found autoantibodies to muscarinic receptors in another disease of orthostatic intolerance called idiopathic postural hypotension. In a small 2016 study, Dubey’s findings suggested the same was true for POTS – bringing the number of possible cardiovascular system-affecting autoantibodies in POTS to six.
“We Have A Potential For a Therapy”
The big news from Kem’s talk was the real potential for a therapy – and not just a therapy which moves the needle a bit, but one which gets at the core of the disease. Here again, POTS researchers proved to be moving faster than ME/CFS or FM researchers. Neither ME/CFS nor fibromyalgia has an animal model, but at the conference, Kem reported that an animal model of POTS has been created.
Kem has a novel treatment – a decoy peptide which causes the autoantibodies to bind to it instead of the damaged receptors. Using a mouse-sized tilt table, Kem tested the decoy peptide in the animal model and it worked – the mice experienced no heart rate increases when taking a tilt table test.
Roadblock
Kem proclaimed, “We now have a potential for a therapy”, but he has hit a legal roadblock. It turns out that just two sentences in another patent described a similar method of using a “peptide decoy”. Despite the fact that the other patent didn’t test the idea or fully explicate it in the patent, the patent office is, thus far, denying Kem’s patent application – which he will need to raise money for the study.
Kem’s patent application for a novel therapy for POTS hit a roadblock, but he hopes to get back on track in about 6 months.
An appeal is underway and should be complete within 6-8 months. If successful, it will take a year to test the decoy peptide in laboratory animals. If that’s successful, a Phase II safety and efficacy study in humans would probably take two years. If that works out, then come the big Phase III studies; we’re looking at a minimum of five years, if everything goes smoothly, before a drug could come to market. If it does make it, though, it could be a very effective treatment for POTS.
Kem is putting his focus on getting treatments to POTS patients first, and the antibody tests he’s using are not available commercially yet. Kem, though, appears absolutely sure that POTS is, at least in large part, an autoimmune disease. He believes all postulates needed by Witebskey’s Postulates for the presence of an autoimmune disorder have been fulfilled.
From the discovery of perhaps six autoantibodies that are whacking away at the cardiovascular systems of POTS patients, to a potential treatment that appears, at least thus far, to work in an animal model, the POTS field, small as it is (the NIH didn’t even track POTS spending until recently), has been moving fast.
Next up, a Mayo MD talked about an autoimmune disease he believes is greatly underdiagnosed in POTS, how he treats the autoimmunity he finds in POTS, the role he believes MCAS plays, and more.
Autoimmunity, Sjogren’s Syndrome, Mast Cell Activation Syndrome and POTS – Brent Goodman MD
Brent Goodman is a Mayo Clinic doctor hailing from Phoenix, Az who gets it. He came to talk about the complex situation regarding autoimmunity, MCAS, POTS and treatment.
Some clues indicating that you may have an autoimmune condition include: acute onset, infectious onset, immunization onset, family history of autoimmunity, significant and rapid weight loss, onset during pregnancy – many of which we see in POTS, ME/CFS and/or FM.
It’s a complex field. Unfortunately, most autoantibody tests lack specificity. (Ron Davis’s lab is working on better antibody tests). Plus, as Grubb noted in his earlier presentation, more than one autoantibody is usually present in an autoimmune disease. (Eight to ten are apparently present in rheumatoid arthritis. Thus far, about six have been associated with POTS, and more may be present in ME/CFS).
The presence or absence of autoantibodies may not, however, correlate with disease activity, and autoantibody treatment may not result in reduced symptoms. Major fluctuations in symptoms in diseases like Sjogren’s Syndrome can obscure treatment effects. You get the feeling that while medical science has made strides with treating some autoimmune diseases, it’s still struggling to get a handle on them.
Sjogren’s Syndrome – The All Purpose Disorder
Goodman highlighted Sjogren’s Syndrome (SS). When you look for SS in POTS, he said, you will find it. He believes it’s an important part of POTS.
Sjogren Syndrome (SS) is a subject that’s near and dear to my heart – my mother didn’t have ME/CFS, but she eventually died of complications from Sjogren’s in her fifties.
SS is known for the dry eyes and mouth it often – but not always – produces, but it also has a predilection for affecting the autonomic nervous system. In fact, Goodman is so taken with the autonomic nervous system symptoms SS produces that he and his co-authors wrote in a recent study that: “A diagnosis of Sjögren Syndrome should be aggressively pursued in patients with signs and symptoms suggestive of autonomic nervous system impairment.”
That small study suggested that autonomic problems run rampant in Sjogren’s Syndrome. All the participants reported lightheadedness, fainting or near fainting upon standing. Over half of his patients displayed exaggerated heart rates or increased blood pressure upon standing. Plus, the gastrointestinal and/or urinary symptoms so often present in POTS and ME/CFS were found in almost all the participants, and gut motility was impaired in 5/6 patients who underwent testing.
If your symptoms fit Sjogren’s and you have a negative antibody test, you still need a lip biopsy to rule Sjogren’s Syndrome in or out.
Goodman is not the only one to notice the Sjogren’s autonomic nervous system connection. A larger Korean study found that autonomic problems were common in Sjogren’s and were associated with increased fatigue. An even larger 2012 UK study and a 2008 Swedish study suggested the same.
Sjogren’s Syndrome – which was mentioned again and again at the conference – could be causing your POTS or ME/CFS-like symptoms. In fact, Goodman, who called Sjogren’s an all-purpose disorder, said that if you can think of a neurological condition, Sjogren’s can cause it.
The good news is that if you do happen to have Sjogren’s Syndrome – instead of or in addition to POTS or ME/CFS – treatment possibilities are available: Goodman reported that three Sjogren’s Syndrome patients in his study who received immune therapy (IVIG or IVIG+Rituximab) improved significantly. After treatment, two of them no longer experienced any autonomic nervous system symptoms such as problems standing.
Getting Tested
Getting diagnosed with SS requires either positive antibody blood tests OR a positive minor salivary gland biopsy. Doctors who rely on antibody tests in combination with dry eyes/mouth to diagnose SS are behind. About 40% of Sjogren’s patients don’t have the SS-A or SS-B antibodies, Some never experience dry eyes or mouth. Dysautonomia International notes that younger SS patients with neurological symptoms may be more likely to have negative antibody tests. SS can affect the autonomic nervous system without producing either.
- Check out the American-European SS criteria here.
Mast Cell Activation Syndrome (MCAS)
Goodman was another presenter at the conference who was very high on mast cell activation syndrome (MCAS). He believes MCAS is a common downstream consequence of Sjogren’s Syndrome. He gave another twist to the autoantibody findings in POTS when he reported that the adrenergic antibodies found in POTS can also activate mast cells.
Lauren Stiles (Dysautonomia International founder), whose tortured path to her SS diagnosis can be found below, noted that her mast cells were going bananas until she got IVIG and then they quieted down.
Goodman recommends MCAS treatment whether testing is positive or not if the symptoms fit the bill. (He treats the patients – not the lab results).
Goodman noted that GI dsymotility (movement issues – either slowed or increased) are greatly underappreciated and can be severe in POTS. They can affect the gut (digestive problems) and/or the esophagus (swallowing problems) and require feeding tubes, resulting in hospitalization. He’s also finding that Cromolyn works great for gastrointestinal symptoms.
Autoimmune diseases can produce so many symptoms that diagnosis can take a while. Goodman remembered a 36 year old woman diagnosed by a Mayo doctor with “adjustment disorder”, whom he, another Mayo doctor, later found to have POTS. She had indications of autoimmunity and he treated her with IVIG and methylprednisone and she quickly recovered. He wondered if early treatment (which rarely happens) could make a big difference. In people with Sjogren’s Syndrome and POTS, he reported that IVIG has an 83% success rate (!).
Treatment can be tricky, though. Goodman described a Sjogren’s Syndrome patient who responded to IVIG, recovered, played sports again, and then developed a bad case of dry eyes/mouth and started producing antibodies to Sjogren’s.
Goodman usually uses subQ immunoglobulin (SCIG, 0.4 grams/kg weekly) instead of IVIG in chronic conditions because of the risk of developing aseptic meningitis and because of headache problems.
Goodman also uses methylprednisolone (1 g IV x 1-2 d.) instead of prednisone. The potential for the chronic side effects associated with prednisone use are minimal with methylprednisone. He also uses Rituximab a fair bit.
Conference Overviews
- 2018 Dysautonomia International Conference I: Small Fiber Neuropathy, POTS, MCAS and Vagus Nerve Stimulation
- The 2018 Dysautonomia Conference Pt. II: Could You Have a Spinal Fluid Leak? An ME/CFS, POTS, FM Perspective
Thanks to Dysautonomia International for their support attending the conference.
Next Up – An Entirely Different Kind of POTS – Hyperadrenergic POTS
Your Support Keeps the Information Coming
Thanks for the coverage Cort!
Since I’m in a research study – I had all these autoimmune things tested (that Kem was talking about and also Sojourns testing) and all were okay for me. Yet we know there are autoimmune factors at play. My POTS is in generations of our family. Mine is different than others in my family and seems to be more complex. (Or maybe I’ve just had more testing.) It’s encouraging that some may be able to get help this way though. I was just talking to one of my friends who does subQ and Rituxian. She isn’t completely well – but has her life back. (I’m sooooo happy for her!!!!)
MCAS treatment was a turning point for me. It has definitely helped and GastroCrom has worked wonders. Terribly expensive! Glad to have had insurance.
Issie
Glad to hear it Issie. The kind of general thing I got from the autoimmunity talks is that its a complex subject and there’s still quite a bit of grey area. Another thing was the increasing interest in MCAS. Too bad that treatment is really expensive!
Yeah it is too bad it is so expensive. I don’t think there is much competition to bring the price down. There are few using (as its sooooo expensive) so they sort of have a niche/monopoly. Sad for those who it would help and they can’t get it. If hubby retires or we lose insurance…..I’ll be in huge trouble without it. I guess we will cross that bridge then. Today has its own issues and things can change. It was a big turning point for me. I’m glad Goodman is treating people regardless of labs. I think we may not have sensitive enough test (or enough knowledge/science) to concretely have data. Sometimes better to use educated experience and knowledge and if it makes sense – try it. If it helps – yayyyyyy. If it doesn’t, that’s something ruled out.
Issie
Dear Issi,
I wouldn’t have the nearly normal life I live without cromolyn sodium but I refuse to pay the outrageous price for Gastrorom even if my insurance company will pay for it. This is an old, very inexpensive drug that has been simply repackaged and renamed. Walgreens bought out a compounding pharamacy and certain Walgreens (I am in Ocala, Florida) have the ability to compound Cromolyn Sodium in nonallergenic capsules (mine are 200mg) and depending where you live this will cost roughly $85 for a 30 day supply (at 4 x a day). Because our insurance stupidly doesn’t cover the compounded form, Walgreens, recognizing this, gave us their discount price since we purchase our other meds there. I think the regular price is around $115.
Cort, thank you for continually giving us hope!!
Nice article Cort
Thanks
Thanks again Cort for your fantastic blogs 🙂
This i like: ‘The increased levels of stress hormones needed to compensate would likely leave POTS patients “wired and tired”.
Finally i have the answer of my one milion dollar guestion here 🙂
Yes. Me too – finally an answer or at least one answer for that mysterious problem.
Thanks Cort, do u know if this new drug for POTS will also work for orthostatic issues in ME/CFS that aren’t POTS but dysautomania of some sort?
I don’t know. Kem stated, if I wrote it down correctly, that the peptide decoy would soak up three of the antibodies present in POTS I assume that ME/CFS would need to have those antibodies for the decoy to work. On the other hand, if they can build a decoy for those antibodies why not a decoy for other ones?
This is a brand new treatment approach with all that entails but Kem seemed quite hopeful. I got the feeling talking to him that one way or another the patent problem is going to be resolved. There are several ways to do that – the best being having the patent office reverse its decision.
Was there any indication about how much longer it will be until the blood tests for these auto antibodies for POTS will be available to the public? Waiting is difficult!
I didn’t get any indication of that unfortunately. My notes indicated that he said it was a difficult process. The more studies that come out though which successfully use those autoantibody tests the better the chances would be I would think.. Kem believes these autoantibodies are at play in other diseases. Hopefully that will spur more work.
I do want to point out that Kem’s work was funded by a large number of parties from European and Swedish groups to the NIH to Dysautonomia International. Hopefully, his and others work is catching on and he and others interested in this aspect of POTS will get more and more funding and the field will move forward faster and faster.
The good news from the day before was that Grubb announced that a large still unpublished study backed up Kems and others autoantibody findings.
Thank you for your as always, very interesting articles, but I seem to be missing part III.
Ha! So is everyone else, including me. Until you mentioned this I didn’t realize that I had jumped from Pt 2 to Pt 4. I changed the title – this is Pt 3 and Pt. 4 is coming up.
Thanks for keeping me from having two part IV’s (lol).
I can’t help thinking that “training” our children’s young bodies (that were designed to practice all these automatic responses to standing and walking while growing) to sit for hours every day in classrooms when their body’s natural way of being is to be up and walking.. somehow stops the body “learning” the natural processes and causes long term damage to the body
I would not be surprised at all! Who knows what damage – besides the type II diabetes epidemic – is occurring by not engaging in the exercise the body needs and expects when young.
Agreed
Cort:
I’ve been sick 10 years with ME/CFS – now I’m 66 and having high blood pressure issues that are not under control. My doc thinks it’s related to my autonomic issues. My blood pressure was low before I got sick. Was this problem discussed at the meeting?
Chris Williams
It was probably mentioned. The thing is that that these 6 (or who knows perhaps more autoantibodies) can probably produce so many permutations. Check this Medscape article out – https://www.medscape.com/viewarticle/543590_4
It refers to this study (https://www.ncbi.nlm.nih.gov/pubmed/?term=hyperadrenergic+POTS+mast+cells) which indicates that almost 40% of POTS patients with mast cell activation also exhibit orthostatic hypertension – high blood pressure upon standing. It appears to be associated with hyperadrenergic POTS which the last blog on the conference will cover.
Do you experience flushing? Has the possibility of MCAS been assessed. From the study abstract.
“In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 119+/-7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P<0.05)."
"In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.
I’ll have to contact one of my friends about where the lab is – I think in Germany. She had her antibodies tested there. I think in the States it’s just in research labs from what I understand.
You’re correct about some of us having high blood pressures with hyperPOTS. It’s considered more rare. But I’m one. I have variable pressure with drastic swings. Can’t treat highs because of lows and vice a versa. It’s difficult to manage. Many of us with Hyper presentation also have MCAS and EDS. We call it the trilogy.
Issie
The Trilogy!
Cort, as you stated here regarding Sjogren’s testing, “Getting diagnosed with SS requires either positive antibody blood tests OR a positive minor salivary gland biopsy.” I can tell you first hand it is more nuanced than that.
In 2018 I had a blood draw that was done in house (Ocshner-Baton Rouge) and sent out to a lab in Los Angeles. In both labs anything above 20 was considered positive. At the in-house lab my blood showed 7.59. At the Los Angeles lab it was 87!! A very strong positive. SAME BLOOD!
I was diagnosed with CFS in 2008. To this day my ANA is negative. I think with the diagnosis of CFS and the negative ANA they did not care to dig further. They did not care to send to a more specialized lab. It was not until 2017 and a lot of work on my part (paying to go to Workwell, etc.) that they got more serious.
The test was the Sjogren’s test for SSA and SSB. My numbers cited are for the SSA portion.
Wow. That doesn’t inspire confidence. As I remember Lauren Stiles – diagnosed with SS after a lip biopsy -and with no elevated ANA readings either – is an IVIG responder. Really a tricky area.
TRea
Hi Cort, I too have have never had an elevated ANA but after reading your article on Lauren Stiles I pushed for a lip biopsy. That came back positive from our local pathologist. But then when we further pursued getting in w a neuro Sjogren Dr, their testing of the same biopsy did not meet their criteria. So do I have Sjogrens or not??
“After treatment (IVIG/IVIG w Rituximab) they no longer experienced POTS symptoms” Cort, do you know how much treatment this entailed?
Hezza: As we have all learned, medicine is as much art as it is science. It has been shocking to me to see how subjective medicine is. I have found myself stating a theory about ME/CFS to my doctors and in my head I say, “And anything about to come out of your mouth is a theory too.” Of course I don’t say that, but I am thinking it.
Because I know the answers are not there yet so when A doctor says something about ME/CFS (or even my diagnosed Sjogren’s or my diagnosed Antisynthetase Syndrome) like it is fact I am very suspicious.
Thank you for this interesting article. The various diagnostic labels don’t seem to match reality. Over the past 15 years of illness I have had every possible combination of low, normal, and high blood pressure (both supine and standing) along with low, normal and high heart rates, and low, normal and high pulse pressures. So for me, the labels are useless while the entire medical industry revolves around the all-powerful diagnostic code.
Currently my BP is always low and worse while standing while my heart rate depends on… the day of the week? the phase of the moon?
The one constant in my ever more frequent episodes of orthostatic intolerance is that the longer I stand the worse the symptoms become. Meanwhile the local doctors prefer to fill my record with psychobabble rather than try to find out what is actually wrong with my physiology. I despair of ever finding competent treatment.
A big question I have about the autoimmune hypothesis is, where is the tissue damage? As I understand it, the whole purpose of an antibody is to mark the cell for destruction, such as is seen in rheumatoid arthritis, for example. Since there are cells with adrenergic receptors everywhere, it should be easy to find damage, but I don’t recall any research papers that discuss the issue at all.
What am I missing?
Wow. One study states that hypertension upon standing can end up with low blood pressure upon standing. That symptom the longer you stand the worse it gets could also be spinal fluid leak – with that the longer you’re up and the later in the day – the worse the symptoms which can mimic POTS and usually feature a headache.
https://www.healthrising.org/blog/2018/07/21/dysautonomia-conference-cerebral-spinal-fluid-leak-pots-me-cfs-fibromyalgia/
I don’t about receptor damage. Researchers have found damage to a loop in the adrenergic receptor but you’re getting molecular there – no overt sign of physical damage I imagine.
“A big question I have about the autoimmune hypothesis is, where is the tissue damage?… …Since there are cells with adrenergic receptors everywhere”
Didn’t I read in the blog on the Cortene theory / drug test that part of it is that plenty new receptors (for some hormone in that case) are grown?
If so, adrenergic receptors marked with antibodies might be “trimmed” and replaced by new ones too? A bit like mowing the grass; replacement is so common that the grass field looks pristine while near all grass has been cut in height.
Add on top of that that many (types of) muscle cells, like in smooth muscle cells in blood vessels, are replaced at a relative high rate (removing previous damage). Inflammation, which is going to go hand in hand with auto-immunity also creates plenty of some growth factor stimulating new blood vessel growth replacing entire damaged capillaries.
I believe the faster damaged tissue is replaced, the harder it may be to catch auto-immunity in action. Sickness then may come from the cost of the continuous cycle of immune activation – destruction – repair rather then from parts of the body being damaged and no longer functional.
Also the function may be altered. In the example of the grass mown: both a pasture and a garden patch of grass look healthy under normal conditions. But one can withstand arid periods for far longer than the other.
Thank you so much, Cort. This is fantastic info. Is it okay if I share it with my doc? I think he’d find it very interesting/useful. (He’s a very open, functional medicine MD.)
Of course ?
Encouraging to see this progress but the years long wait for the treatment is discouraging as I am now 70 and have been dealing with cfs and pots since 1989. I had been dealing with a big crash and flare after the flu since 2008 and most recently been largely bed bound with elevated heart rate since October of 2017 which the cardiologist blames on Pots. My ANA has been 320 for years with no definitive Auto immune disease diagnosis. Pots possibly being auto immune gives me some explanation. Any ideas of what can be done besides keeping hydrated with salt in water in the meantime?
I find abdominal compression to be helpful. I got a neoprene exercise band to go around my mid section and wear it over a tank top and under my clothes. If I have to sit for a long length of time compression socks are good to help avoid blood pooling.
Issie
Thanks for the suggestion, Issie! where would you suggest the best place to go for evaluation for Pots. I went to the university of Chicago in 2010 and was told that I was too old to have pots as it is a disease of mostly young adults and that for them it resolves. My cardiologist, of course , does not agree but has no real expertise in pots let alone CFS. His suggestions have been hydration and possible evaluation at Mayo. I have had years of bad experiences and no help so I am reluctant to go there as I remember reading about other CFS patients unsatisfactory experiences there. I tried getting an appointment with Blair Grubb in Ohio, but the wait was a year. My symptoms seem to be getting worse which may just be my immune system declining with age.
My doc is Dr Brent Goodman at Mayo in AZ. I trust him. He is not judgemental and listens. I wasnt DX until I was in my 40s, but had it most of my life. It is however, very expensive to go to Mayo. You will reach your max out of pocket. He is also now on the Dysautonomia International board. He has been doing more lectures recently.
Issie
Hi, thank you for the information. I have had a very positive response to SSRI (Sertraline). It has improved my pots extremely. I could hardly walk before, had extremely fatigue and brain fog, used a wheelchair everywhere etc today, just four weeks after, I could walk throw a store, ride on my electric bike, cooking my own food, my sleep is better, less fatigue etc it has given me my life back! I also take Mestinon and Betablockers.
Has anyone here had their blood tested at CellTrend in Germany for their POTS-related autoantibody panel?
http://www.celltrend.de/cfs-diagnostics.html
It’s my understanding that, as of a few years ago at least, they were the only commercial lab testing for the same kinds of autoimmune markers that are showing up in the latest research on autoimmune-mediated POTS. (Including several of the same ones highlighted in Cort’s article here.)
Are they still the ones to use?
(I realize the results would be for informational purposes only, and not formally diagnostic.)
Thanks!
That’s the only one I know of. The labs in the States are only doing them in research settings from what I can find out.
Issie
Thanks Issie! That’s what I am seeing as well, but I’m glad to have some confirmation. 🙂
WOW most interesting article to date for me! A lot makes sense! Most I read either is contradicting, has no clarity at all,this actually gives me hope at least and that is something. I know it’s not something that may come fast but after fight advanced breast cancer 9 years I’ve built patience. If anyone reads this, if your platelets have ever dropped fast due to any of this (POTS/Sjogren’s Syndrome) can you please let me know. I’m concerned it’s my cancer but hard to find out when your cancer center of 9 years doesn’t return phone calls in 2 weeks!
It’s very interesting to me to discover (some years behind!) that Dr Goodman sometimes uses prednisolone. I was recently prescribed prednisolone for an allergic rash, and it coincidentally fixed my orthostatic intolerance symptoms, not only while I was taking it, but also for months afterwards. My symptoms gradually returned to baseline. Now I’m wondering whether I have Sjogren’s syndrome that’s not yet detectable.