Autoimmune Testing Back From Mayo - Any Idea Of What Presence Of "calcium Channel Binding Antibody, N-Type" Means?

[kitt]

Sue1234,

Sorry! I didn't mean 'you' personally at all! Just have had people insist that all hyper pots patients have high BP, and while that's usually true, it's occasionally not true.

As to the autoimmune testing Mayo does. It is not one, two or three tests. There are at least ten different tests including:

Anti-neuronal Nuclear Ab

N type Calcium channel

Achr Ganglionic neuronal Ab

Etc....

Don't have a link yet.

Here is a link though that describes symptoms associated with AAG.

http://rarediseasesnetwork.epi.usf.edu/ARDCRC/patients/learnmore/AAG/

[Guest Alex]

Out of curiosity, for those of you who tested positive for the AChR antibody, how elevated were your titers? From what I read these titers are supposedly low in POTS.

Thanks,

Alex

[kitt]

Thank you Diabeticgonewild for sharing your treatment protocol.

I had plasmapheresis done many years ago. My husband was the donor. Are you using a donor or are they using your own blood?

How lucky you are to have a neurologist who understands how to treat you!

Is it someone local or someone from a big clinic, like CC, Mayo or elsewhere?

How are you responding to treatment?

[diabeticgonewild]

Out of curiosity, for those of you who tested positive for the AChR antibody, how elevated were your titers? From what I read these titers are supposedly low in POTS. Thanks, Alex

I am not going to give out a specific value, but mine were < 1.0 nmol/L.

[diabeticgonewild]

Thank you Diabeticgonewild for sharing your treatment protocol.

I had plasmapheresis done many years ago. My husband was the donor. Are you using a donor or are they using your own blood?

How lucky you are to have a neurologist who understands how to treat you!

Is it someone local or someone from a big clinic, like CC, Mayo or elsewhere?

How are you responding to treatment?

I have no donor, as far as I know. The replacing fluid is albumin. My blood cannot be used, as it has antibodies.

I don't see anyone from a big clinic. I see a neurologist in Houston that specializes in neuromuscular diseases.

I have never seen Vernino. I don't see the point of doing that. I would have to go to Dallas every 2-3 weeks at least.

I am responding poorly to treatment in my opinion. I get better and worse. Overall, I think I am getting better, from my worst point.

I have been unable to work and I applied for disability.

[Guest Alex]

Out of curiosity, for those of you who tested positive for the AChR antibody, how elevated were your titers? From what I read these titers are supposedly low in POTS. Thanks, Alex

I am not going to give out a specific value, but mine were < 1.0 nmol/L.

thanks, I'll send you a PM.

Alex

[kitt]

Vernino now works with Ben Levine and the two of them were unable to find the a3 acetylcholine nicotinic receptors in any pots patients.

Rama, Perhaps Vernino was unable to find a3 acetylcholine nicorinic receptors in pots patients, but Mayo has.

Pasting:

The pathophysiology has been well characterized owing to the discovery of nicotinic ganglionic acetylcholine receptor antibodies in patients with AAG, though at least half of cases presents without detectable autoantibodies.

Here's the link.

http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P03.024

[Guest Alex]

Kitt,

AAG stands for autoimmune autonomic ganglionopathy - not the same thing as POTS.

the titres of the AChR ab are much more elevated in AAG than those found in some POTS patients.

If you read the symptoms associated with AAG - one of them is the blunted HR (lack of variability in HR - that's quite the opposite in POTS)

I think rama is strictly talking about POTS.

Alex

[Guest Alex]

Miqual, sorry we're hijacking your thread

[kitt]

Kitt,

AAG stands for autoimmune autonomic ganglionopathy - not the same thing as POTS.

the titres of the AChR ab are much more elevated in AAG than those found in some POTS patients.

If you read the symptoms associated with AAG - one of them is the blunted HR (lack of variability in HR - that's quite the opposite in POTS)

I think rama is strictly talking about POTS.

Alex

Alex, I understand what AAG stands for.

It's an autoimmune issue that can be found in pots patients. I posted the symptoms of AAG.

Here's the description under Autonomic Disorders Consortium. http://rarediseasesnetwork.epi.usf.edu/ARDCRC/patients/learnmore/AAG/

And from another study, (Dr. Low at Mayo)

Pasting:

Approximately 50% of cases report an acute or subacute onset, often following a viral illness, suggesting an immune-mediated process. In a recent review (Thieben, 2007) of 152 cases of POTS seen consecutively by Sandroni and Low, 6 of 42 patients (who had ganglionic antibody measured) had increased levels of antibody.

Link:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671239/

AAG is a rare disease, but it is one of several forms of autoimmune disorders that can be associated with pots.

Alex, I'm not suggesting that pots and AAG are the same thing. I'm talking about people with pots who also have ganglionic antibodies, thus indicating an auto immune form of pots.

Best,

K

[Guest Alex]

Miqual, and everyone else

here is an article that might interest you - full text - about those Calcium channel antibodies

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739271/pdf/nihms123352.pdf

happy reading,

Alex

[ramakentesh]

Vernino now works with Ben Levine and the two of them were unable to find the a3 acetylcholine nicotinic receptors in any pots patients.

Rama, Perhaps Vernino was unable to find a3 acetylcholine nicorinic receptors in pots patients, but Mayo has.

Pasting:

The pathophysiology has been well characterized owing to the discovery of nicotinic ganglionic acetylcholine receptor antibodies in patients with AAG, though at least half of cases presents without detectable autoantibodies.

Here's the link.

http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P03.024

Hi Kitt

Dr Vernino was THE doctor at Mayo that identified (among others) the acetylcholine a3 nicotinic autoantibodies firstly in obvious cases of orthostatic hypotension and then it was suggested in some POTS patients. The work was published but critics of the paper suggested that the number of POTS patients that exhibited these autoantibodies were low (10-13%) and more importantly the titer levels in the POTs patients tested were TINY.

All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology. As an example Ankylosing Spondylitis patients have over 150 weird autoantibodies floating around, most inactive.

Subsequent to publishing the early study on the a3 autoantibodies in POTS, Dr Theiben published anotehr paper suggesting that because of the presentation of POTS it is likely autoimmune.

But then another major research group were unable to find the a3 nicotinic autoantibodies in any POTS patients. And when Dr Vernino left Mayo and was hired by Ben Levine's group in Texas they were unable to replicate the previous results - that is the same doctor from Mayo who identified the a3 nicotinic receptor autoantibodies and implicated them in POTS was unable to replicate those results.

So AAG and POTS remain seperate entities.

And of even more interest was the fact that a Mayo related student published to more recent papers on new autoantibodies in POTS but all the patients in the cohort had profound orthostatic hypotension, excluding them from a diagnosis of POTS according to the recent consensus statement.

[ramakentesh]

Kitt,

AAG stands for autoimmune autonomic ganglionopathy - not the same thing as POTS.

the titres of the AChR ab are much more elevated in AAG than those found in some POTS patients.

If you read the symptoms associated with AAG - one of them is the blunted HR (lack of variability in HR - that's quite the opposite in POTS)

I think rama is strictly talking about POTS.

Alex

Exactly.

[ramakentesh]

In relation to Mayo there is some interesting information being offered by a doctor on one of the major POTS-related facebook pages. A doctor claims that Mayo now send may of their POTS patients to him because they 'cant treat them'

[kitt]

i Kitt

Dr Vernino was THE doctor at Mayo that identified (among others) the acetylcholine a3 nicotinic autoantibodies firstly in obvious cases of orthostatic hypotension and then it was suggested in some POTS patients. The work was published but critics of the paper suggested that the number of POTS patients that exhibited these autoantibodies were low (10-13%) and more importantly the titer levels in the POTs patients tested were TINY.

All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology. As an example Ankylosing Spondylitis patients have over 150 weird autoantibodies floating around, most inactive.

Subsequent to publishing the early study on the a3 autoantibodies in POTS, Dr Theiben published anotehr paper suggesting that because of the presentation of POTS it is likely autoimmune.

But then another major research group were unable to find the a3 nicotinic autoantibodies in any POTS patients. And when Dr Vernino left Mayo and was hired by Ben Levine's group in Texas they were unable to replicate the previous results - that is the same doctor from Mayo who identified the a3 nicotinic receptor autoantibodies and implicated them in POTS was unable to replicate those results.

So AAG and POTS remain seperate entities.

And of even more interest was the fact that a Mayo related student published to more recent papers on new autoantibodies in POTS but all the patients in the cohort had profound orthostatic hypotension, excluding them from a diagnosis of POTS according to the recent consensus statement.

Hi Rama,

As I said, I'm very familiar with the fact that pots and AAG are separate identities.

Am going to stand behind the links I've already posted, and let them speak for themselves.

Mayo has a panel of over ten different antibodies that they check for in pots patients looking for an autoimmune cause to pots.

To your point that, (Quoting you) "All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology"

Absolutely true! Thank you for making that point. Many, many times people have low titers of antibodies, and Mayo will be to the first to tell you this is 'an incidental finding', and not meaningful. Mayo is very quick to find all sorts of anomalies in their exhaustive, and I mean exhaustive! testing, and I know firsthand they consider many of those anomalies, (including low levels of various antibodies to all sorts of things) to be 'incidental findings', and not meaningful.

Rama, I've been to Mayo more times than I can count, and have had several major surgeries there. To suggest that a pots-related Facebook page has a doctor claiming (quoting you) that Mayo now send may of their POTS patients to him because they 'cant treat them' seems absurd to me.

Am curious to see the Facebook page please?

Mayo is far from perfect, but it's one of the finest diagnostic facilities in the world, and many of us have not only been treated there, but been helped tremendously by Mayo. I know you're not in the US, but Mayo is in a class unlike any other.

Also regarding hypotension...You're saying hypotension rules out pots? Not in my case. I have hypotension and I have hyper pots. Not unique. Unusual but not unique.

Am guessing you agree that many pots patients have an autoimmune etiology?

Some of us with other autoimmune illnesses have good reason to suspect we may well have an autoimmune basis for our pots.

When I was dx with Hashimoto's years ago by Mayo they told me that it put me at greater risk for developing Addison's 'later on'. When a person is dx with one autoimmune disease, it increases their risk of developing others.

Thanks for sharing Rama. Let's try and move forward and share data that may help others looking for information on autoimmune pots data.

Best,

K

[diabeticgonewild]

POTS is a syndrome, which is a diagnosis fit for no underlying disease cause.

AAG is a disease and is a primary cause of progressive autonomic failure.

If you have AAG, there's no point in referring to your tachycardia as POTS, because the underlying disease is known.

When people apply for disability due to POTS, they encounter a lot of problems due to the diagnosis being a syndrome. The SSA treats syndrome diagnosis differently than diseases and it is significantly more difficult to prove disability due to POTS.

If anyone needs any further clarity regarding this issue, look up the differences between a syndrome and a disease.

[ramakentesh]

i Kitt

Dr Vernino was THE doctor at Mayo that identified (among others) the acetylcholine a3 nicotinic autoantibodies firstly in obvious cases of orthostatic hypotension and then it was suggested in some POTS patients. The work was published but critics of the paper suggested that the number of POTS patients that exhibited these autoantibodies were low (10-13%) and more importantly the titer levels in the POTs patients tested were TINY.

All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology. As an example Ankylosing Spondylitis patients have over 150 weird autoantibodies floating around, most inactive.

Subsequent to publishing the early study on the a3 autoantibodies in POTS, Dr Theiben published anotehr paper suggesting that because of the presentation of POTS it is likely autoimmune.

But then another major research group were unable to find the a3 nicotinic autoantibodies in any POTS patients. And when Dr Vernino left Mayo and was hired by Ben Levine's group in Texas they were unable to replicate the previous results - that is the same doctor from Mayo who identified the a3 nicotinic receptor autoantibodies and implicated them in POTS was unable to replicate those results.

So AAG and POTS remain seperate entities.

And of even more interest was the fact that a Mayo related student published to more recent papers on new autoantibodies in POTS but all the patients in the cohort had profound orthostatic hypotension, excluding them from a diagnosis of POTS according to the recent consensus statement.

Hi Rama,

As I said, I'm very familiar with the fact that pots and AAG are separate identities.

Am going to stand behind the links I've already posted, and let them speak for themselves.

Mayo has a panel of over ten different antibodies that they check for in pots patients looking for an autoimmune cause to pots.

To your point that, (Quoting you) "All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology"

Absolutely true! Thank you for making that point. Many, many times people have low titers of antibodies, and Mayo will be to the first to tell you this is 'an incidental finding', and not meaningful. Mayo is very quick to find all sorts of anomalies in their exhaustive, and I mean exhaustive! testing, and I know firsthand they consider many of those anomalies, (including low levels of various antibodies to all sorts of things) to be 'incidental findings', and not meaningful.

Rama, I've been to Mayo more times than I can count, and have had several major surgeries there. To suggest that a pots-related Facebook page has a doctor claiming (quoting you) that Mayo now send may of their POTS patients to him because they 'cant treat them' seems absurd to me.

Am curious to see the Facebook page please?

Mayo is far from perfect, but it's one of the finest diagnostic facilities in the world, and many of us have not only been treated there, but been helped tremendously by Mayo. I know you're not in the US, but Mayo is in a class unlike any other.

Also regarding hypotension...You're saying hypotension rules out pots? Not in my case. I have hypotension and I have hyper pots. Not unique. Unusual but not unique.

Am guessing you agree that many pots patients have an autoimmune etiology?

Some of us with other autoimmune illnesses have good reason to suspect we may well have an autoimmune basis for our pots.

When I was dx with Hashimoto's years ago by Mayo they told me that it put me at greater risk for developing Addison's 'later on'. When a person is dx with one autoimmune disease, it increases their risk of developing others.

Thanks for sharing Rama. Let's try and move forward and share data that may help others looking for information on autoimmune pots data.

Best,

K

Mayo do have a panel "dysautonomia panel' that they often use on POTS patients - however only a few of them have been demonstrated to be pathological and none have been proven and there is minimal evidence that they are pathological in POTS.

that doesnt mean that POTS isnt autoimmune or that most POTS patients who exhibit many characteristics of autoimmunity (such as abrupt onset, 80% female, relapsing remitting, comorbid autoimmune diseases) - evidence is strong that in many it may be an autoimmune process, but there is no compelling published evidence that demonstrates that the specific autoantibodies on the MAYO panel are involved in the etiology of POTS in any cases.

Yeah i just posted that Dr Alo's comments for a laugh.

Doctors commonly diagnose all orthostatic intolerance syndromes with tachycardia as POTS but compensatory tachycardia can occur in postural hypotension and according to the recent consensus statement significant postural hypotension excludes from the diagnosis of POTS - you can email Blair Grubb or Julian Stewart and ask them. But patient forums are full of people with postural hypotension who have been diagnosed with POTS by other doctors and since the understanding of the undlerying etiology of either is unclear who knows whether its correct or not. Personally i dont think its that relevant. Similar to the break up of hyper v non hyper - its basically a useless delineation in terms of working out the underlying cause - although it might help with treatment.

What I think is the most compelling work connecting autoimmunity with POTS is related to the neuropathic POTS variant. If you have a systemic autoimmune disease and you have POTS then according to some doctors you DONT actually have POTS - you have autonomic neuropathy. But its the same illness I hear you say? Exactly... What I tend to find and what docs tend to tell me is that most with POTS and comorbid autoimmune conditions seem to also exhibit abnormal QSART results or signs of patchy small fiber neuropathy.

In diabetes and sarcoidosis it has been proven that patients ewith these conditions who have OI symptoms and small fiber neuropathy have neuropathy of the autonomic sympathetic nerves of the smooth muscle (IE wider autonomic involvement). But no one has yet proven this to be the case in POTS with SFN or POTS that appears with other autoimmune diseases. But its probable.

Anyone who has an autoimmune disease and POTS should get a QSART test or skin biospy because it may open doors to treatments like IVIG which many do very well on.

Hope that makes sense as im on a train...

[ramakentesh]

POTS is a syndrome, which is a diagnosis fit for no underlying disease cause.

AAG is a disease and is a primary cause of progressive autonomic failure.

If you have AAG, there's no point in referring to your tachycardia as POTS, because the underlying disease is known.

When people apply for disability due to POTS, they encounter a lot of problems due to the diagnosis being a syndrome. The SSA treats syndrome diagnosis differently than diseases and it is significantly more difficult to prove disability due to POTS.

If anyone needs any further clarity regarding this issue, look up the differences between a syndrome and a disease.

I wonder how they go with AIDS. its a syndrome

[ramakentesh]

The funniest thing about this whole discussion is that in recent years mayo have adopted the position that chronic cases of pots are sustained by somatic hypervigilance and symptom catastrophising. All while a student from there publishes works identifying new autoantibodies in pots against cardiac remodeling proteins and then cardiac raft cells.

there pediatric program where they tell the parents of children with pots that if they buy in to the physical nature of their child's illness then the child will be more disabled and that the child nerds to ignore their symptoms to improve (ie force them to go to school, etc) is certainly a new and interesting direction.

you can read all about in the notes for the talks from the 2012 autonomic symposium. And people found the grinch syndrome controversial.. At least it had SOME evidentiary basis.

[Guest mattgreen]

Rama, what would a skin biopsy/qsart show in excess of an already diagnosed AI disease that would lead to a higher likelihood of treatment with IVIG? Sorry if you've answered this before.

[ramakentesh]

It could be and is often used to suggest wider autonomic involvement as a manifestation of the autoimmune disease as in some small fiber neuropathy with signs of autonomic involvement has been proven to be a sign of wider sympathetic denervation.

[Shellee]

Hi Miqual,

I found the DINET site and your question today when searching for information for my daughter.  i note that you posted your question in 2013. Do you have any updated information that you can share? 

My daughter was diagnosed with dysautonomia in 2014 at the age of 13.   She completed a dysautonomia autoimmune panel in December 2014. (Mayo) and we learned she had calcium channel - N-type, but our doctors at Children's Hospital did not know what to make of it, as we are not seeing any indication of LEMS.  We were told VGCC-n-type sometimes shows up in dysautonomia, but they don't know why.  We spent a month at Mayo in 2015, including several weeks at the Pediatric Pain Rehabilitation Center.  Despite following Levine Protocol and doing following every recommendation for POTS, her symptoms have continued to worsen.  We retested for the autoimmune panel this July (2017), and the Mayo test came back almost identical in titer value to 2014.  Our autoimmune neurologist said the #s would be significantly higher if my daughter were paraneoplastic.  No signs of LEMS,   She just completed testing for chronic encephalitis . I'm grateful for all the "normal" and "negative" results, but we still have no answers.  In the past few weeks, she has undergone a lumbar puncture and autoimmune panel for encephalitis, Brain and Lumbar MRIs. 

My daughter started IVIG therapy in November with her immunologist.  We have not seen any improvement. It has been suggested that we consider Rituximab  and/or Cellcept.  I'm uncomfortable with these options. 

Thank you for your time.  I'd appreciate any insight re: voltage-gated calcium channel - N-type and Dysautonomia.

Shellee