Lolinda
J'aime nager dans le froid style Wim Hof.. 🏊♀️🙃
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In POTS, OH and CFS, antibodies against adrenergic and muscarinic receptors can contribute to the disease by binding to the receptor and cause it to malfunction. See also here. It is now possible to test this. I got tested. So from my experiences, I will describe in this post where to get tested and how to send the sample.
This thread is for questions and ideas regarding: labs, tests, sample sending, etc. There are separate threads for:
Wonder why I create separate threads for these? I just hate it to browse through threads of 30 pages talking about everything on earth often not related to the thread title. Takes hours. So this is my little initiative to have small threads that answer exactly one specific question. You need some information and you get exactly that. I also support a lot @Hip 's idea for a clever search that finds the most relevant posts.
Simple introduction
What is all this about?
When a nerve sends a message to a muscle or another nerve, then at the end of the nerve, a chemical is released. On the receiving muscle or nerve, there is a receptor that listens to these chemical messages. An autobody is not a nice thing, because it binds to the receptor, so the receptor won't hear the message. It is like talking to somebody wearing ear plugs. Now, these ear plugs are around in the body and if they find an ear (a receptor), they block it. It is also possible that they activate it permanently. This messes up a communications between nerves and parts of the body. A common misconception is that people think these antibodies would destroy nerves or such, as in other autoimmun diseases. These dont.
Concretely, which receptors are we talking about?
I found this diagramm by @halcyon useful. It contains a simple way of structuring all these receptors: there are adrenergic and cholinergic receptors. The adrenergic receptors divide into alpha-adrenergic and beta-adrenergic receptors. The cholinergic receptors divide into muscarinic-cholinergic (or simply muscarinic) and nicotinic-cholinergic (or simply nicotinic) receptors. If you wonder what this adrenergic, cholinergic, muscarinic and nicotinic is about: adrenergic means that the respective receptors are stimulated by adrenaline or noradrenaline, that is stress hormones. Cholinergic receptors are stimulated by the neurotransmitter acetylcholine. Now the cholinergic receptors divide into two types: some are, in addition to acetylcholine, also stimulated by nicotine, others are also stimulated by muscarine.
And now you become the medical pro by learning technical abbreviations...
:
Adrenergic and muscarinic receptors are divided into enumerated subgroups:
A1, A2, B1, B2, M1, M2, M3, M4, M5
These are short names, where A1 stands for "Alpha 1 adrenergic receptor", B1 for "Beta 1 adrenergic receptor", M1 for "muscarinic cholinergic 1 receptor". As all this post is about antibodies, I will not always write "A1 antibody" but simply "A1".
What the heck do all these receptors do?
They all have a myriad of different functions, just look up some on wikipedia. It is much about vasoconstriction, vasodilation, and heart beating. How antibodies to these receptors contribute to POTS, OH or CFS is discussed here.
- If things still remain unclear, let me know what you want to know.
Which antibodies to test for which disease?
My decision was to get tested for all A1, A2, B1, B2, M1-5. However, in order to save cost, it is possible to restrict to the most relevant ones depending on your issues: see this thread. In any case, this is a hot area of research where new publications are coming out. So if today the relevance of an antibody is not yet known, maybe in a month it is. -> Better test all.
Where to get tested - commercial
I know only one commercial lab:
http://www.celltrend.de/
Trustworthiness:
Their tests are the ones used by Prof. Scheibenbogen, CFS researcher at the Charite Berlin, a premier academic medical institution in Germany. Actually, they developed the tests together. Just search for Celltrend in this paper.
So, this is why I trust them.
BUT: Be patient with them:
They are a research lab usually serving other researchers. They are in the process of opening up to private customers, but things are simply not yet that smooth as one would expect it. For me, being a researcher, it is really not an issue. I wrote this post to help all others who want to do these tests but do not have the experience to do so. In my opinion it is better to have a not-so-smooth process but a professional test than otherwise round. There are so many questionable labs on which no researcher would trust even the blood of their lab mice, but sending in samples and receiving results is super smooth, giving you the utmost false impression of professionalism...
Tests:
See the requisition forms attached to this post. Unfortunately, one of the most important antibodies for POTS (A1, see this thread) is also the most expensive. They explained me that adrenergic antibodies need different chemical reagents than the rest.
Requisition + blood draw:
Their new requisition form for all these tests is not yet online, so I attached it to this post, in English and in German. Blood draw instructions for the lab are at the bottom of the requisition form.
Prescription:
You do not need a prescription and you do not need to involve any doctor at all. You can fill out the requisition form yourself. You pay directly to Celltrend, they invoice you. All you need to get done by a local lab is the blood draw. There are further important things on the blood draw. I give these details below, messed into my shipping instructions.
Shipment:
Celltrend receive samples from allover the world. However, their international shipment instructions for private customers are not yet ready. I did similar international sample sendings several times. So here is how I sent the samples to them. I give you all details, but actually it all boils down to a few phone calls, optionally a doctors visit, a lab visit, 2 papers filled out and receiving a Fedex guy at your door.
Additional test for better interpretation of the results:
The Celltrend tests only measure if there are antibodies. They do not answer the question if your antibodies are agonistic or dysfunctional. That is, if they activate or block the receptor. The importance of this is discussed here , for POTS, OH and CFS. Unfortunately, if you wish to find out which of these happens at your receptors, things get tricky: you need a "rat cremaster assay":
What that means? Kill a rat and use the reaction of a still living artery from their testicles as a measurement device... Poor rats... I am not aware of any commercial lab offering this, let alone if every testicle artery of every rat behaves the same... But maybe the following could be useful: Activation of the beta receptors increases cAMP in plasma, see this research.
Labs testing for cAMP in plasma:
There are problems with such measurements, because other factors than receptor autoantibodies can elevate cAMP. But if beta adrenergic receptor autoantibodies are elevated then more likely than not a high or low cAMP will indicate agonistic or dysfunctional beta receptor antibodies, respectively.
To say it clearly, this cAMP testing is my own and fully experimental idea. Comments welcome! Nevertheless testing could have additional interest because cAMP blocks the innate immune system. Thanks to @Emootje for all the discussions on cAMP.
Where to get tested - research
If you are lucky, you also may have a chance to get tested at a research center. For example, you could get included in a scientific study. This has advantages such as that you do not have to pay and that you meet doctors who are knowledgeable in interpreting the results. So here I collected the research centers I know of.
Prof. Scheibenbogen, Charite, Berlin, Germany.
CFS researcher. Her research:
Prof. Angela Vincent, Oxford, can measure adrenergic receptor antibodies. Her research:
and
Dr. Satish Raj,Vanderbilt University
Their research (POTS and OH):
I thank a lot to @Research 1st , @kangaSue , @Freddy @Hip @Emootje, @Gingergrrl and many others for all the links, discussions and your interest, in PMs or on the original thread.
This thread is for questions and ideas regarding: labs, tests, sample sending, etc. There are separate threads for:
- Pathomechanisms: How the antibodies contribute to POTS, OH or CFS
- Doctors & treatment chances
- People who already got tested post their results and their symptoms so we can learn from it (yet to be created! I am currently looking for further people who would be ready to share their results. PM me on this! The main purpose of such a thread would be to see not only one but different results, compare and discuss)
Wonder why I create separate threads for these? I just hate it to browse through threads of 30 pages talking about everything on earth often not related to the thread title. Takes hours. So this is my little initiative to have small threads that answer exactly one specific question. You need some information and you get exactly that. I also support a lot @Hip 's idea for a clever search that finds the most relevant posts.
Simple introduction
What is all this about?
When a nerve sends a message to a muscle or another nerve, then at the end of the nerve, a chemical is released. On the receiving muscle or nerve, there is a receptor that listens to these chemical messages. An autobody is not a nice thing, because it binds to the receptor, so the receptor won't hear the message. It is like talking to somebody wearing ear plugs. Now, these ear plugs are around in the body and if they find an ear (a receptor), they block it. It is also possible that they activate it permanently. This messes up a communications between nerves and parts of the body. A common misconception is that people think these antibodies would destroy nerves or such, as in other autoimmun diseases. These dont.
Concretely, which receptors are we talking about?
I found this diagramm by @halcyon useful. It contains a simple way of structuring all these receptors: there are adrenergic and cholinergic receptors. The adrenergic receptors divide into alpha-adrenergic and beta-adrenergic receptors. The cholinergic receptors divide into muscarinic-cholinergic (or simply muscarinic) and nicotinic-cholinergic (or simply nicotinic) receptors. If you wonder what this adrenergic, cholinergic, muscarinic and nicotinic is about: adrenergic means that the respective receptors are stimulated by adrenaline or noradrenaline, that is stress hormones. Cholinergic receptors are stimulated by the neurotransmitter acetylcholine. Now the cholinergic receptors divide into two types: some are, in addition to acetylcholine, also stimulated by nicotine, others are also stimulated by muscarine.
And now you become the medical pro by learning technical abbreviations...
:Adrenergic and muscarinic receptors are divided into enumerated subgroups:
A1, A2, B1, B2, M1, M2, M3, M4, M5
These are short names, where A1 stands for "Alpha 1 adrenergic receptor", B1 for "Beta 1 adrenergic receptor", M1 for "muscarinic cholinergic 1 receptor". As all this post is about antibodies, I will not always write "A1 antibody" but simply "A1".
What the heck do all these receptors do?
They all have a myriad of different functions, just look up some on wikipedia. It is much about vasoconstriction, vasodilation, and heart beating. How antibodies to these receptors contribute to POTS, OH or CFS is discussed here.
- If things still remain unclear, let me know what you want to know.
Which antibodies to test for which disease?
My decision was to get tested for all A1, A2, B1, B2, M1-5. However, in order to save cost, it is possible to restrict to the most relevant ones depending on your issues: see this thread. In any case, this is a hot area of research where new publications are coming out. So if today the relevance of an antibody is not yet known, maybe in a month it is. -> Better test all.
Where to get tested - commercial
I know only one commercial lab:
http://www.celltrend.de/
Trustworthiness:
Their tests are the ones used by Prof. Scheibenbogen, CFS researcher at the Charite Berlin, a premier academic medical institution in Germany. Actually, they developed the tests together. Just search for Celltrend in this paper.
So, this is why I trust them.
BUT: Be patient with them:
They are a research lab usually serving other researchers. They are in the process of opening up to private customers, but things are simply not yet that smooth as one would expect it. For me, being a researcher, it is really not an issue. I wrote this post to help all others who want to do these tests but do not have the experience to do so. In my opinion it is better to have a not-so-smooth process but a professional test than otherwise round. There are so many questionable labs on which no researcher would trust even the blood of their lab mice, but sending in samples and receiving results is super smooth, giving you the utmost false impression of professionalism...
Tests:
- There is a dedicated page for a reduced set of antibodies most relevant for CFS.
- The complete list of all their receptor antibody tests A1, A2, B1, B2, M1, M2, M3, M4, M5 can be found here. This is the list of tests that I had done.
See the requisition forms attached to this post. Unfortunately, one of the most important antibodies for POTS (A1, see this thread) is also the most expensive. They explained me that adrenergic antibodies need different chemical reagents than the rest.
Requisition + blood draw:
Their new requisition form for all these tests is not yet online, so I attached it to this post, in English and in German. Blood draw instructions for the lab are at the bottom of the requisition form.
Prescription:
You do not need a prescription and you do not need to involve any doctor at all. You can fill out the requisition form yourself. You pay directly to Celltrend, they invoice you. All you need to get done by a local lab is the blood draw. There are further important things on the blood draw. I give these details below, messed into my shipping instructions.
Shipment:
Celltrend receive samples from allover the world. However, their international shipment instructions for private customers are not yet ready. I did similar international sample sendings several times. So here is how I sent the samples to them. I give you all details, but actually it all boils down to a few phone calls, optionally a doctors visit, a lab visit, 2 papers filled out and receiving a Fedex guy at your door.
- First, call Celltrend and ask for their Fedex Number. Thats all what you need from them in advance. No need for any test kit.
- Call Fedex and ask them about delivery options to Celltrend, Germany. Celltrend specifies the following possibilities:
- 24h shipment is fine in any weather
- 72h shipment is fine when there are normal room temperatures outside. It is not ok in hot summer with 30°C
- 96h shipment is fine in a cold pack (4°C)
Fedex will tell you what of these they can offer from your location. The 24h shipment is a particularly attractive option as it is available from many locations at no additional charge.
- You may want to make sure the transport is done at "international priority" rates, which are the normal rates.
- Fedex will come to you. Ask which is the latest pickup time. Here where I Iive, pickup times are specified as 2h windows within which the Fedex guy comes to your door. For the 24h delivery, they have special pickup times that are earlier than for normal delivery.
- After all these preparations, arrange with a doctor / lab for the blood draw. For all the A1, A2, B1, B2, M1-5 tests, you need 1 serum tube in total, no more. Important: make sure in advance that the specific lab office you will be visiting can produce the serum right there in the office. They need a machine for that, a centrifuge. Big labs may have many small blood drawing stations without the machines, which then are in the central lab facility. That won't work for you.
- When in the lab, insist that they centrifuge and separate the blood within 60 minutes after the blood draw. Centrifuging makes the red blood cells collect into a mass. All the remainder will be a yellowish liquid that looks like pee Separating means that they transfer the serum into a separate tube which then contains only the serum.
- Make sure your name and date of birth is on the tube
- Now call Fedex to pick up the sample. Ask for a "clinical pack". That is a special packaging. They will ask you if sending on dry ice is needed. You don't need that. (And you dont want to pay that!! ).
- Prepare and print out a "proforma invoice" to be sent with the clinical pack to make sure customs don't stop things. If you don't know what that is, ask Fedex. It is a word document of a few lines of text. Prepare it like Fedex specifies. They will tell how many copies.
- Important: The Fedex guy at your door will ask you to fill out a form where you specify Celltrend as the recipient and yourself as the sender. In this form you must mark that the Fedex costs are billed onto the recipients Fedex number and you must specify their Fedex number. (Celltrend will then bill the cost to you together with the costs of the tests. The purpose of this procedure is simply that Celltrend gets cheaper Fedex rates. They have a higher traffic.)
- Ask your doctor if you can get a "flying nurse" service, so you can get blood draw at home and do not need to go to any lab.
- Alternatively, you can reduce effort by cutting out the doctor, see "Requisition" above.
- Instead of interacting with Fedex yourself, you can also have this done for you by some labs. In fact, I made good experiences with this: Not far from me, there are two small, owner-managed labs. They are far more flexible and customer-oriented than big labs. Both were immediately ready to do some international sample sendings for me. All I needed to do is to reassure them that the Fedex costs are not billed onto them but onto the Fedex number of the recipient. Tell them what the latest pick-up time is for your shipment option and provide them with the Fedex number for Celltrend.
Additional test for better interpretation of the results:
The Celltrend tests only measure if there are antibodies. They do not answer the question if your antibodies are agonistic or dysfunctional. That is, if they activate or block the receptor. The importance of this is discussed here , for POTS, OH and CFS. Unfortunately, if you wish to find out which of these happens at your receptors, things get tricky: you need a "rat cremaster assay":
What that means? Kill a rat and use the reaction of a still living artery from their testicles as a measurement device...
Poor rats... I am not aware of any commercial lab offering this, let alone if every testicle artery of every rat behaves the same... But maybe the following could be useful: Activation of the beta receptors increases cAMP in plasma, see this research.Labs testing for cAMP in plasma:
- Dr Stein, Germany
- Synlab Switzerland
There are problems with such measurements, because other factors than receptor autoantibodies can elevate cAMP. But if beta adrenergic receptor autoantibodies are elevated then more likely than not a high or low cAMP will indicate agonistic or dysfunctional beta receptor antibodies, respectively.
To say it clearly, this cAMP testing is my own and fully experimental idea. Comments welcome! Nevertheless testing could have additional interest because cAMP blocks the innate immune system. Thanks to @Emootje for all the discussions on cAMP.
Where to get tested - research
If you are lucky, you also may have a chance to get tested at a research center. For example, you could get included in a scientific study. This has advantages such as that you do not have to pay and that you meet doctors who are knowledgeable in interpreting the results. So here I collected the research centers I know of.
Prof. Scheibenbogen, Charite, Berlin, Germany.
CFS researcher. Her research:
- http://www.sciencedirect.com/science/article/pii/S0889159115300209 This is also the research paper from which you can see why exactly those same antibodies are on the Celltrend CFS panel. And here some PR discussion about this. Here a CFS patient was included in one of her studies - lucky one!
Prof. Angela Vincent, Oxford, can measure adrenergic receptor antibodies. Her research:
- The following paper is not about POTS or CFS but about chronic complex regional pain synrome and is only here to show you that she can measure adrenergic receptor antibodies: http://www.sciencedirect.com/science/article/pii/S030439591400445X However, she does publish also on POTS. So she is likely a good address. (Let me know if you have experiences and I will modify these lines accordingly)
and
Dr. Satish Raj,Vanderbilt University
Their research (POTS and OH):
- http://jaha.ahajournals.org/content/3/1/e000755.full
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259269/
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275920/
- http://www.ncbi.nlm.nih.gov/pubmed/22130180
I thank a lot to @Research 1st , @kangaSue , @Freddy @Hip @Emootje, @Gingergrrl and many others for all the links, discussions and your interest, in PMs or on the original thread.
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