POTS, OH, CFS: List of labs which test for adrenergic and muscarinic receptor antibodies

[Gingergrrl]

I wanted to update that I did the blood draw this morning at a specialty lab and it will be shipped to Cell Trend in Germany via Fedex International later today! It all went well except for the part where they find my vein which took a few tries .

But everything else went smoothly and I had the requisition form, Fedex #, doctor's note, etc, all prepared in advance and am doing all nine of the auto-antibody tests that I mentioned a few posts up. The blood (separated serum) should arrive to Germany in 2-3 days which Dr. Heidecke (the head of the lab) confirmed was okay. Then it should take 1-2 weeks to get my results.

I will post them here as soon as I know and if they are positive, I have to figure out how I want to proceed given all of my other autoantibodies.

 

[halcyon]

But everything else went smoothly and I had the requisition form, Fedex #, doctor's note, etc, all prepared in advance and am doing all nine of the auto-antibody tests that I mentioned a few posts up.

Sorry if I missed it, but is the requisition form attached to the first post in the thread the most up to date one or is there a better one to use?

 

[Gingergrrl]

Sorry if I missed it, but is the requisition form attached to the first post in the thread the most up to date one or is there a better one to use?

The req form in the first post of this thread appears to be the same as the one that I had Cell Trend e-mail to me along with some other information. But the address on both forms (in the thread and the one I received) is different than the address that they had me mail the sample to with Fedex. The addresses are similar but they e-mailed me the one they wanted me to use, the name of the person to put to her attention, plus the Fedex #. I am not sure if I am allowed to publicly post it but happy to give you via PM or e-mail. My suggestion though is to actually have a phone call with them and once I did this, all of my questions were answered.

 

[Gingergrrl]

My blood sample arrived at Cell Trend today and was easy to follow with the Fedex Tracking number. The entire process was fairly simple once I got the missing info. Will post my results when I get them in 1-2 weeks.

I saw my Neuro today and showed her the req form with the nine tests but sadly she was not familiar with them and said she would not know how to interpret them nor would they be of use to her. But that is okay and my main doctor is very interested in the tests now and even ordered them for another patient b/c of me.

So I am hoping that he will help me to interpret them and that I will also contact one of the doctor referrals that I get from Cell Trend. There are only a handful of doctors world-wide who might know what to do with these tests but I will find them...

 

[Lolinda]

Cell Trend told me it does not have to be shipped Overnight and it can take 3-4 days to arrive but this seems strange?

Now, I asked the boss of Celltrend. Here is the outcome:
- 72h shipment is fine at normal room temperatures but not ok in hot summer with 30°C
- 96h shipment is ok in a cold pack (4°C)

I did a 24h shipment in hot summer, without cold pack. 24h shipment is a nice option because from many locations, it is available without any additional cost, at "international priority" rates (i.e. normal Fedex rates).

 

[Gingergrrl]

@Lolinda Mine ended up getting there in a little over 48 hrs with the cold pack so I am pretty sure it was okay. I was not sure of the specifics when I asked about it last week so please disregard any of my other logistical questions!

 

[Gingergrrl]

I wanted to post an update (and will post the details later) but I just got my results back from Cell Trend and I am positive on seven of the nine autoantibodies!!! This shocked even me.

This is quick b/c I have to leave shortly to take my dog back to the vet (she might have cancer) and cannot miss this appt and I also have to be out of my apt bldg the entire day b/c of fire alarm testing before they shut down the elevators and I cannot leave. The torture never ends...

So I will post the specific test results and details later tonight or tomorrow. My Neuro said the tests are of no use to her and is not helping me with getting the higher dose of IVIG but thank you God, my main doctor said these tests are very significant and show that I have an autoimmune disease that is causing me significant Neurological problems and we are going to do a phone consult soon to discuss the IVIG and RTX. He is now testing other patients and said that my work on this will not only help me but also others.

I also re-contacted the head of Cell Trend Labs for referrals to doctors in the US that can help me and my doctor here (but do not have the names yet).

Am tagging a few people who might be interested @Lolinda @Sidereal @zzz @Justin30 @RL_sparky @halcyon (sorry if I am forgetting anyone) and have to leave now for the day.

 

[Gingergrrl]

I am so sorry for not being able to keep up with PR this past week and have over 80 new messages and 13 new PM's
which I plan to read as soon as I can!

My main doctor and Neuro both think I had a seizure yesterday from the fire alarm going off in my unit and most likely a "startle seizure". My husband and best friend witnessed it and were able to describe it to the doctors. I know this is not the right thread to discuss this so will focus on the Cell Trend tests.

Here are my complete results on the nine tests and am hoping someone on PR can help me to interpret them. At the moment, this is the only thread that I will be following. I lied and I am trying to respond to some other threads while I have the opportunity .

Here are all nine of the auto-antibodies and the seven I am positive for are bolded:

1) Anti a1-adrenergic antibodies: Positive at 22.6 (above 7 is positive)

2) Anti a2- adrenergic antibodies: Negative at 12.2 (Positive is above 15)

3) Anti B1- adrenergic antibodies: Positive at 30.4 (above 15 is positive)

4) Anti B-2- adrenergic antibodies: Positive at 18.3 (above 14 is positive)

5) Anti-Muscarinic Cholinergic receptor 1 antibodies: Positive at 13 (above 9 is positive)

6) Anti-Muscarinic Cholinergic receptor 2 antibodies: 9.6 (above 9 is positive) so this one not as extreme.

7) Anti-Muscarinic Cholinergic receptor 3 antibodies: Positive at 24 (above 10 is positive)

8) Anti-Muscarinic Cholinergic receptor 4 antibodies: Positive at 27 (above 7 is positive)

9) Anti-Muscarinic Cholinergic receptor 5 antibodies: Negative at 8.3 (positive is above 14)

---------
If anyone has any feedback on what these mean, I would be eternally grateful. My main doctor feels these test results are extremely important and show significant autoimmune and Neuro dysfunction and that we will learn about them together and hopes they will help my case to get the autoimmune dose of IVIG and later RTX.

My Neuro literally refused to look at them b/c they were not US tests and were experimental in her mind and said they were of no use. I whole-heartedly disagree with her and I know they are of value.

I am also positive for the N-type calcium channel Ab and for the anti GAD65 Ab in case this is relevant and am really starting to think my POTS is autoimmune and that every aspect of my illness is autoimmune and that I might have SPS (Stiff Person Syndrome). I am getting sicker and cannot figure out what to do if I cannot get the autoimmune dose of IVIG which I am certain is the next step.

ETA: In case this helps, I have now had four doses (one every 3-4 weeks) of low dose IVIG at 24 grams and it has put my MCAS into remission. But the autoimmune dose starts for me at 55 grams and could even go over 100 grams (in a split dose of course). Insurance only approved me for the lower 24 grams which clearly pushed my immune system away from the allergic reactions but it is not enough to affect the autoantibodies. I will literally do anything for the opportunity to try the higher dose and cannot begin to explain the level of effort I am putting into this battle.

 

[daisybell]

Wow @Gingergrrl ... so many auto-antibodies. Do you think your doctors might consider trying rituximab sooner rather than later?
I don't have any useful advice or info but just want to say I'm keeping all my fingers and toes crossed for you...

 

[Gingergrrl]

Wow @Gingergrrl ... so many auto-antibodies. Do you think your doctors might consider trying rituximab sooner rather than later?

Yes and I will be having a phone consult with my doctor in two weeks unless I can get a sooner appt. He was sent a copy of the results from Cell Trend and knows what is going on. If I can get RTX, I am 100% on board. I wish I had a local doctor on board but am doubtful this will occur.

ETA: Thank you @daisybell for your support.

 

[halcyon]

Anti a1-adrenergic antibodies: Positive at 22.6 (above 7 is positive)

2) Anti a2- adrenergic antibodies: Negative at 12.2 (Positive is above 15)

3) Anti B1- adrenergic antibodies: Positive at 30.4 (above 15 is positive)

4) Anti B-2- adrenergic antibodies: Positive at 18.3 (above 14 is positive)

This matches the Kem et al. autoimmune POTS findings 1 2:

POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR-mediated tachycardia. Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia.

5) Anti-Muscarinic Cholinergic receptor 1 antibodies: Positive at 13 (above 9 is positive)

6) Anti-Muscarinic Cholinergic receptor 2 antibodies: 9.6 (above 9 is positive) so this one not as extreme.

7) Anti-Muscarinic Cholinergic receptor 3 antibodies: Positive at 24 (above 10 is positive)

8) Anti-Muscarinic Cholinergic receptor 4 antibodies: Positive at 27 (above 7 is positive)

9) Anti-Muscarinic Cholinergic receptor 5 antibodies: Negative at 8.3 (positive is above 14)

The M1 and M2 antibodies have been found in POTS, and the M1, M3, and M4 have been found in CFS patients in various studies. Nobody has reported finding M5 autoantibodies as far as I know, so this would generally match as well.

 

[Gingergrrl]

This matches the Kem et al. autoimmune POTS findings:

@halcyon So the David Kem findings show an elevated a1AR, β1AR and β2AR and these all correlate with POTS and these are the ones that I have? Do they ever mean anything separate from POTS or would you say that these tests are basically measuring the autoimmune form of POTS? I have absolute confirmation of POTS from two TTT's but would you say that these tests show that I have an autoimmune form of POTS? Nothing you can explain is too basic for me and I really appreciate it.

The M1 and M2 antibodies have been found in POTS, and the M1, M3, and M4 have been found in CFS patients in various studies. Nobody has reported finding M5 autoantibodies as far as I know, so this would generally match as well.

So the muscarinic/cholinergic Abs that I have either correlate with POTS again or have been found in ME/CFS patients? Do they ever mean anything else?

Do you know why these tests are offered in Germany but not in the US? Is it a money/pharma reason?

 

[halcyon]

So the David Kem findings show an elevated a1AR, β1AR and β2AR and these all correlate with POTS and these are the ones that I have?

Exactly.

Do they ever mean anything separate from POTS or would you say that these tests are basically measuring the autoimmune form of POTS? I have absolute confirmation of POTS from two TTT's but would you say that these tests show that I have an autoimmune form of POTS? Nothing you can explain is too basic for me and I really appreciate it.

It's consistent with what's been found so far, I think that's all we can say right now.

So the muscarinic/cholinergic Abs that I have either correlate with POTS again or have been found in ME/CFS patients? Do they ever mean anything else?

Yes. I'm not sure where else these are found, it looks like there is an association with Sjogrens.

 

[Gingergrrl]

Thank you @halcyon and I plan to investigate if any of these antibodies are correlated with other autoimmune diseases (LEMS, Stiff Person Syndrome, ion channelopathies, etc) but have not gotten that far yet.

Do you know if the autoimmune form of POTS would be treated in a different way than a non-AI form? I watched (and posted) a video last week from Dysautonomia International re: IVIG potentially helping POTS and I assume they meant the autoimmune form?

 

[halcyon]

Do you know if the autoimmune form of POTS would be treated in a different way than a non-AI form? I watched (and posted) a video last week from Dysautonomia International re: IVIG potentially helping POTS and I assume they meant the autoimmune form?

Right now, I don't believe so, the standard autoimmune treatments would apply. What's cool is that Kem is working on a drug that would act as a decoy and neutralize the antibodies in the blood, but this would probably take years to become available if it ever does.

 

[Gingergrrl]

Right now, I don't believe so, the standard autoimmune treatments would apply. What's cool is that Kem is working on a drug that would act as a decoy and neutralize the antibodies in the blood, but this would probably take years to become available if it ever does.

So it would be autoimmune treatments vs. dysautonomia treatments for this type of POTS? Do you have any links re: this drug that Kem is working on? I have heard about him but clearly need to start researching him more and am not even sure where he is located or if he sees patients or is strictly a researcher? Thank you so much again.

ETA: Would the decoy to neutralize the Abs be similar to the concept of IVIG?

 

[halcyon]

So it would be autoimmune treatments vs. dysautonomia treatments for this type of POTS?

The drugs currently used off label for POTS target the same receptors that these antibodies do. Beta blockers block the beta adrenergic receptors, so they likely stop the agonist autoantibodies from binding instead and this reduces the tachycardia/palpitations. Alpha agonists like midodrine stimulate the alpha adrenergic receptors that the autoantibodies are partially blocking, so perhaps this slightly works around the blockade and gives you some vasoconstriction. The obvious treatment though would be to remove the offending autoantibodies, and this is done with the current immunosuppresive treatments.

Do you have any links re: this drug that Kem is working on? I have heard about him but clearly need to start researching him more and am not even sure where he is located or if he sees patients or is strictly a researcher? Thank you so much again.

He's in Oklahoma. He discusses the drug starting around 33:00 in his recent talk at the Dysautonomia International conference.

ETA: Would the decoy to neutralize the Abs be similar to the concept of IVIG?

Not sure since we don't know how IVIG works for autoimmune disease in the first place. The drug causes the antibodies to bind to it instead of our own receptors.

 

[Gingergrrl]

The drugs currently used off label for POTS target the same receptors that these antibodies do. Beta blockers block the beta adrenergic receptors, so they likely stop the agonist autoantibodies from binding instead and this reduces the tachycardia/palpitations. Alpha agonists like midodrine stimulate the alpha adrenergic receptors that the autoantibodies are partially blocking, so perhaps this slightly works around the blockade and gives you some vasoconstriction. The obvious treatment though would be to remove the offending autoantibodies, and this is done with the current immunosuppresive treatments.

Wow, for some reason, I did not totally grasp this until right now even though it has been explained to me a million times. No wonder Atenolol and Midodrine work so well for me. I get it that they are just masking the problem and since I started IVIG in July, I stopped the Midodrine but I have not been able to stop the Atenolol, it just is not possible. ITA with you that finding something to remove the offending autoantibodies is the goal and if there is a way to do it, I will find it. (ETA: I don't mean that I will create it, but if it exists, I will hunt it down and find it).

He's in Oklahoma. He discusses the drug starting around 33:00 in his recent talk at the Dysautonomia International conference.

Thank you and I just bookmarked this post and plan to watch his talk that you linked tomorrow. Am going to Google him and am curious if he consults with patients and/or their doctors or is strictly research.

Not sure since we don't know how IVIG works for autoimmune disease in the first place. The drug causes the antibodies to bind to it instead of our own receptors.

Although this is not based on anything scientific, I feel that IVIG somehow must thin out the auto-antibodies in the plasma, temporarily giving them less power and ideally replacing them with healthy ones from donors. I had thought IVIG was from 1,000 donors but my doctor said it is more like 20-100,000 donors per batch. Some how it has also modulated my immune system away from the crazy allergic reactions. But I agree that a pill that would cause the antibodies to bind to it instead of the receptors would be ideal if it ever occurs in our lifetime.

 

[Sidereal]

I am so sorry for not being able to keep up with PR this past week and have over 80 new messages and 13 new PM's
which I plan to read as soon as I can!

My main doctor and Neuro both think I had a seizure yesterday from the fire alarm going off in my unit and most likely a "startle seizure". My husband and best friend witnessed it and were able to describe it to the doctors. I know this is not the right thread to discuss this so will focus on the Cell Trend tests.

Here are my complete results on the nine tests and am hoping someone on PR can help me to interpret them. At the moment, this is the only thread that I will be following. I lied and I am trying to respond to some other threads while I have the opportunity .

Here are all nine of the auto-antibodies and the seven I am positive for are bolded:

1) Anti a1-adrenergic antibodies: Positive at 22.6 (above 7 is positive)

2) Anti a2- adrenergic antibodies: Negative at 12.2 (Positive is above 15)

3) Anti B1- adrenergic antibodies: Positive at 30.4 (above 15 is positive)

4) Anti B-2- adrenergic antibodies: Positive at 18.3 (above 14 is positive)

5) Anti-Muscarinic Cholinergic receptor 1 antibodies: Positive at 13 (above 9 is positive)

6) Anti-Muscarinic Cholinergic receptor 2 antibodies: 9.6 (above 9 is positive) so this one not as extreme.

7) Anti-Muscarinic Cholinergic receptor 3 antibodies: Positive at 24 (above 10 is positive)

8) Anti-Muscarinic Cholinergic receptor 4 antibodies: Positive at 27 (above 7 is positive)

9) Anti-Muscarinic Cholinergic receptor 5 antibodies: Negative at 8.3 (positive is above 14)

---------
If anyone has any feedback on what these mean, I would be eternally grateful. My main doctor feels these test results are extremely important and show significant autoimmune and Neuro dysfunction and that we will learn about them together and hopes they will help my case to get the autoimmune dose of IVIG and later RTX.

My Neuro literally refused to look at them b/c they were not US tests and were experimental in her mind and said they were of no use. I whole-heartedly disagree with her and I know they are of value.

I am also positive for the N-type calcium channel Ab and for the anti GAD65 Ab in case this is relevant and am really starting to think my POTS is autoimmune and that every aspect of my illness is autoimmune and that I might have SPS (Stiff Person Syndrome). I am getting sicker and cannot figure out what to do if I cannot get the autoimmune dose of IVIG which I am certain is the next step.

ETA: In case this helps, I have now had four doses (one every 3-4 weeks) of low dose IVIG at 24 grams and it has put my MCAS into remission. But the autoimmune dose starts for me at 55 grams and could even go over 100 grams (in a split dose of course). Insurance only approved me for the lower 24 grams which clearly pushed my immune system away from the allergic reactions but it is not enough to affect the autoantibodies. I will literally do anything for the opportunity to try the higher dose and cannot begin to explain the level of effort I am putting into this battle.

I know that the IVIG has been hugely successful MCAS-wise for you but I get the impression that your autonomic nervous system reactions to other things like sounds have gotten dramatically worse since starting IVIG. Could there be a link?

 

[Gingergrrl]

I know that the IVIG has been hugely successful MCAS-wise for you but I get the impression that your autonomic nervous system reactions to other things like sounds have gotten dramatically worse since starting IVIG. Could there be a link?

I don't think so b/c I have only tried the IVIG at the lower immune deficiency dose so far and am nowhere near the autoimmune dose. My symptoms have been getting worse for a long time with the startle reflex actually starting about a year and a half ago. My worst symptoms (dyspnea and chest pain) pre-date the IVIG for 2-3 years.

My Neuro finally wrote the note this morning to increase the IVIG to the autoimmune dose so all three docs are in agreement. We think it is possible that I am having increased startle reflex (and one possible startle seizure) b/c of the GAD65 Ab and now we are rethinking Stiff Person Syndrome (and IVIG is also the treatment for this). A third test just confirmed that I still have the Ab (and I first showed this Ab five months prior to starting IVIG) and probably had it even longer than that but just didn't know it. IVIG at the autoimmune dose could reduce this Ab but at the ID dose, would not be expected to.

Since starting IVIG my arm strength is stronger (I can cut papers with scissors and even staple papers which shocked me) and can bring dishes from table to kitchen- all using wheelchair of course. My ability to breathe, stand, walk has not changed but we are hoping with the autoimmune dose of IVIG that this could improve. It definitely does something to modulate the immune system but I have not had the opportunity yet to try even the bottom of the autoimmune dose.

I think my startle reflex was worsening regardless and if anything the increased IVIG and hopefully later RTX (if I can get these things, still have no idea) will be my best shot. I have so many proven autoantibodies now, it is shocking and we want to try to reduce them (without hardcore immunosuppressants that are dangerous or increase cancer risk) and see what happens. We think the autoantibodies are causing the dysautonomia and other Neuro problems. The bottom line is that no one knows for sure, and the science is just not there. So I will be a bit of a guinea pig but it is with informed consent and am trying to learn as much about these new autoantibodies as possible.

And the improvement in the MCAS should equal reduced histamine levels and hopefully allow me to tolerate fluid better. But even with the increased dose of 55 grams, it would be over two days so I would receive 1/4 liter the first day and then 1/4 liter the second day and each one would be given over 6-7 hours. We think I can tolerate this amount which is insanely slower than probably anyone else on earth would get but with the pre-meds and slow speed, we have figured out what works for me. I feel it is my best shot if I can get it approved.