Antibodies to ß adrenergic and muscarinic cholinergic receptors in patients with CFS

[Gingergrrl]

@Gingergrrl , You have also tried a phosphodiesterase (PDE) inhibitor off @Hip's list of pulmonary vasodilators, Pentoxifylline is in that family of PDE inhibitors.

Thanks, KS, and I didn't remember how that med was classified. You are totally correct and I did try Pentoxyfilline and not only did it not help but it dropped my BP further and gave me a horrible headache. I tried it for several days to give it a fair chance until the doctor told me to stop.

 

[Lolinda]

It was debated back and forth by multiple doctors whether my VQ scan in Sept 2014 (when my breathing really started to decline and prior to this was still walking and driving) whether I had a ventilation/perfusion or V/Q mismatch

maybe the following will be all trivial... but as you do not mention this simple investigation for perfusion / ventillation mismatch, I just write it down for the unlikely case that it is not done yet. A further caveat is that all this helps only in case that the perfusion / ventillation mismatch means too much perfusion or too little ventillation. (otherwise round it wont help).


Have you had standing-laying SpO2 done?

You can do it at home with a cheap device. This saves you from
- allergy causing dyes
- doctors who do not understand your disease


What is SpO2 and why is it important?

just as a simple introduction for people reading this and not yet familiar with the topic:
SpO2 is the measure of how many % of oxygen is carried by the RBC compared to full saturation (100%).
if breathing is not adequate to oxygenate all the blood flowing through your lungs, or blood is flowing too fast through the lungs, then you will have a low SpO2.
<95% is hypoxemia:
http://www.ncbi.nlm.nih.gov/pubmed/12135174
<89% is bad hypoxemia:
http://www.ncbi.nlm.nih.gov/pubmed/17709927
this is where organ damage starts on the very long run.
I just got interested in this topic because my polyneuropathy worsens on this. Any other organ will suffer damage on the long run, too. see the discussion here. unfortunately, they do not cite research:
https://healthunlocked.com/blf/post...n-level-is-damaging-other-organs-of-the-body-.
I did not find autoritative numbers on this, various sources cite various numbers such as <92% or <90% or <89%. But the SpO2 devices are anywise not that accurate:
http://www.ncbi.nlm.nih.gov/pubmed/25978517

Then there is a second threshold, where organ damage starts within hours. I think that is around 85% or 80%, and then there is a third limit where one has damage immediately.


Using SpO2 for diagnosis

SpO2 is interesting and highly diagnostic, because in some diseases it gets better upon standing, in others worse. For example in me, SpO2 gets better upon standing (95%), while laying worse (89%). Also, in me it sometimes fluctuates strongly between these two values. These two facts are diagnostic for the situation where a vasodilator coming from another organ enters the lungs. It causes there the blood vessels to dilate -> flow resistance decreases -> blood flows too fast through the lungs, compared to the oxygenation capacity (which is lightly reduced in me but would not cause any probs in itself).
Which vasodilator is the culprit?


Excessive vasodilators as contributors to POTS, OH and low SpO2

Here is my list how to test for various vasodilators.
http://forums.phoenixrising.me/index.php?threads/pots-relief-could-it-be.42775/page-5#post-752424

This is relevant for POTS and OH in general, because vasodilators can make these diseases much worse, independently of any good or bad SpO2.
But vasodilators are also a culprit for mismatch of ventilation and perfusion. For the latter, the main suspect is usually nitric oxide from the gut, but the pathomechanism does not at all rely on NO, but simply on vasodilatation in the lung.
NO is usually elevated in cirrhosis and other liver diseases (hepatopulmonary syndrome), but I do not have that. So I do not know from which organ my vasodilator comes. Possibly the gut, because I have a low SMA resistance index, but then it is unclear why, as I have no liver issues. See here for more on intestinal blood flow:
http://forums.phoenixrising.me/inde...blood-flow-standing-laying.45909/#post-746572


How to test for SpO2

SpO2 is very simple to measure. For a first measurement, any pulmonologist can give an SpO2 meter for a day. Then, if positive and you want to test regularly: Buy an SpO2 meter. Spend a tiny bit more money so you get one with nightly recording and export to PC. I bought this one:
https://www.amazon.co.uk/Wrist-pulse-oximeter-PULOX-PO-400/dp/B003ITM3WI
It is cheap and stupid chinese crap and I would have loved to invest a 100 bucks more. but it is the only one I found that has:
- nightly recording (this is so important because at night spo2 can drop badly)
- export to PC (so you can print out and show doctors)
- is in the form of a wrist watch (this is the only form that is practical for nightly recording. I would not buy anything that hangs on your phone, because what happens if you turn around in bed. equally not anything that only clings to your finger because it will get out during the night)

The drawbacks are:
- does not cooperate with mac, so mac users need parallels
- is user unfriendly
- the software connecting it with the pc is extremely difficult to use
- the device easily switches on when in a bag
- can store only a single recording, so you must export it every single time

in sum: stupid cheap chinese crap.
but all better devices I found are immediately some 1000 bucks. I failed to find a good device for some 200-500 € or $

 

[Hip]

They think my breathing issue is neuromuscular vs. pulmonary and the only med that's helped even slightly from this general category is Midodrine which is a vasoconstrictor vs. dilator.

That shows just how little I know, as I assumed a vasodilator for the blood vessels in the lungs would help, but you are saying a vasoconstrictor helped.

It may not be the vagus nerve as such that is the issue, rather an issue of nicotonic acetylcholine receptors (vagus nerve is a nAChR) which have an influence on mood and behavior (including sickness behavior I believe) through the cholinergic anti-inflammatory pathway. Antibodies to a7- nAChR in this pathway have been reported in the literature but it's one of those ones that doesn't have an accepted commercial test for.

There was a short discussion of the cholinergic anti-inflammatory pathway in this post, which acts as a brake on the innate immune response, and how nicotine can activate this pathway.

 

[Gingergrrl]

That shows just how little I know, as I assumed a vasodilator for the blood vessels in the lungs would help, but you are saying a vasoconstrictor helped.

Or it shows how weird my individual case is?!! They thought Midodrine brought more blood from the feet up to the lungs through "preferential perfusion" but no two doctors really agreed on this. Only that it usually raised my BP out of the 80's/50's and improved my breathing a little. I feel the antibodies are a driving force behind the muscle weakness and dysautonomia in my case although I cannot prove it.

ETA: @Lolinda Am going to reply to your detailed post above when am feeling more alert/awake and thank you for all of the info.

 

[Lolinda]

Or it shows how weird my individual case is?

Not really. Vasoconstrictors oppose the mechanism described above in the long post. In everyone.
Or to put all this super simple:
If you open all the gates of a water reservoir, water will gush out fast like hell. Bad time for fishing!


Or to tell the same in a complicated way:
vasodilators in the lung -> blood vessels dilate, in particular also the capillaries. -> they get thicker
-> 1. the oxygen in the lung needs to travel a longer distance into the thicker capillaries. There will be in the middle of the vessel a lower concentration of oxygen. But the rbc generally tend to be more in the middle of the vessel. (Normally, w/o excessive vasodilatation, a capillary is so thin that an rbc just gets through it. so it is close to the wall, where the oxygen comes from)
-> 2. The blood flows faster, so it is in the lungs for a too short time to get oxygenated

Did you have an SpO2 done?

 

[Lolinda]

My understanding is that autoantibodies can act as receptor agonists or antagonists. If you look at the POTS study, you see that they discovered both agonist and antagonist autoantibodies in POTS (an α1AR agonist, a β1AR antagonist, and a β2AR antagonist).

A late but big thank you for pointing me to this study!! In fact, I have seen this study before, but I just havent noticed that it contains the answer I was looking for (burried in a lot of scientific bla ). So here is my understanding of:
Which adrenergic and muscarinic receptor antibodies bring about or contribute to POTS in some people and how do they do this?

POTS
Here A1, B1 and B2 are elevated. A1 blocks receptors for vasoconstriction. This is a bad thing because when standing up, you need a lot of vasoconstriction otherwise all blood pools into the legs. This is what happens when you see all in black after standing up. If it takes longer, you faint. To avoid this, your sympathetic nervous system (SNS) will try to constrict the blood vessels. This won't work if you have A1 receptor antibodies, which block block vasoconstriction. Hence, the SNS activates more and more, and will try stronger and stronger. Essentially, standing up becomes so stressful as when a healthy person stands in front of a lion. This will make the heart beat more. Here come in the B1 and B2 antibodies, which will make the heart even more prone to tachycardia. The trick is: Receptor antibodies can be agonistic or dysfunctional. So they activate the receptor or switch it off. in POTS, the A1 antibody is dysfunctional, the B1 and B2 antibodies are agonistic:
http://www.ncbi.nlm.nih.gov/pubmed/24572257
http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2012.CE.2.OR48-1
There is a preliminary report on elevated levels of M1 and M2 antibodies in POTS patients, however no mechanism is presented as to how these antibodies contribute to the disease:
http://forums.phoenixrising.me/inde...-with-pots-potential-disease-biomarker.44890/

Does anyone have further papers to add? Further antibodies that may contribute? I have first written this for myself, but thought, I will post this as part of a bigger list of things on how to test for these receptor antibodies, which antibodies and why.

 

[anciendaze]

I haven't read the entire thread, but I want to contribute something concerning Gingergrrl's autoantibodies. Every person I have found who tests positive for antibodies to N-type calcium channels has a pretty clear case of POTS. Her response to beta-blockers was also exaggerated, which makes me suspect she has antibodies to beta adrenergic receptors. We'll know when she is finally tested.

Antibodies to either nicotinic acetylcholine receptors or muscle-specific kinase (MuSK) produce the inhibition of neuromuscular junctions seen in myasthenia gravis. Both these are on the post-synaptic side of the junction, and both have purely negative effects, as do antibodies to N-type calcium channels on the presynaptic side.

The jokers in this deal are antibodies to muscarinic acetylcholine receptors, which can do anything from permanently destroying a receptor to causing it to act like it is constantly on. They can also act like reuptake inhibitors, exaggerating the effect of nerve signals the way SSRIs do with serotonin.

Even when restricted to a single neuromuscular junction the problem is quite complicated. Most doctors pretend there is no interaction between various kinds of impairment, an absurdity.

All these antibodies named above have effects that are not restricted to one particular location. I refer to these as "global" actions. There are entire classes of neurotransmitters which are highly restricted in both time and space, and purinergic neurotransmitters (ATP, ADP, AMP) are among them, as is NO. These are very much involved in vasodilation.

The normal response to hypoxia in a muscle or organ is to release such biochemicals so that blood vessels downstream dilate and increase the pressure drop across the organ. This leads to increased blood flow. The timescale for this response is quite short, on the order of the period of a heartbeat. A number of problems where this does not work correctly now appear to involve constant vasodilation, regardless of exercise. You can't dilate something which is already dilated, and you can't increase blood flow relative to other blood vessels if they are already experiencing the same thing.

The confusing thing about this, in terms of medical specializations, is that it doesn't fit any of them. It is not restricted to the nervous system because red blood cells are often the ones that sense local hypoxia and start the signal cascade by dumping ATP. This doesn't show up in measurements of O2sat because the place you are measuring usually does not have hypoxia. It is hard to measure because things like ATP and NO are reactive, and don't persist long enough to be found where it is convenient to draw blood. It does affect large skeletal muscles, but the problem is primarily with capillaries, where it is again hard to measure.

One other thing, we know there are important ion channels which require more than one chemical signal. (One example shows up with NMDA receptors which need both glutamate and glycine. This has been associated with NMDA receptor autoimmune encephalitis, but only the most spectacular cases are currently being identified.) The ion channels we haven't really pinned down are K+ATP channels which involve both potassium and ATP. Everything about these suggests they are important, but there is a great deal we don't know. If this were not so, we would not still be arguing about the very existence of these vital structures. Defects in the way these function have been implicated in everything from diabetes and ischemia/reperfusion injury in the heart, to say nothing of what they do in the brain. A number of papers concerning these are currently under publication embargo until January 2017. Watch for them.

 

[Lolinda]

Hi @anciendaze interesting post, thanks!

permanently destroying a receptor

I have hard so far on dysfunctional and agonistic muscarinic receptor antibodies. do you have more information on this destroying issue? Any chances to measure this problem?

A number of papers concerning these are currently under publication embargo until January 2017. Watch for them.

huh?? how come?

 

[Gingergrrl]

Am so sorry I haven't got to re-read this thread yet and really want to respond to things from posts by Hip, Lolinda, and anciendaze but won't be able to do it today.

I also haven't had a chance to reply to the email to get the kit to test myself for these auto-antibodies but absolutely intend to do so. I really want to get this info and will share the process in case others want to get tests through the lab in Germany.

Am really far behind with everything from spending all of last week fighting to get my IVIG and all of yesterday getting it. But definitely plan to respond to all of the posts in this really informative thread. Thanks to everyone, and I really mean it, this info is invaluable.

 

[Gingergrrl]

Question for @anciendaze or @Hip or anyone who might know!

Could having IVIG affect the outcome of a test like this to show auto-antibodies (if any of the pooled donors in my IVIG had different antibodies than I do/did)?

My calcium autoantibodies were tested and found pre-IVIG. I am going to attempt to do the blood tests from Germany no matter what but wondered if IVIG could skew my results?

My husband asked me this question b/c my new Neuro (have only seen her once) said that she wanted to run certain tests pre-IVIG b/c my results would never be the same after (these were other tests and nothing to do with the ones from Germany) but how would I know which ones this rule applies to?!!!

 

[anciendaze]

Question for @anciendaze or @Hip or anyone who might know!

Could having IVIG affect the outcome of a test like this to show auto-antibodies (if any of the pooled donors in my IVIG had different antibodies than I do/did)?

My calcium autoantibodies were tested and found pre-IVIG. I am going to attempt to do the blood tests from Germany no matter what but wondered if IVIG could skew my results?

My husband asked me this question b/c my new Neuro (have only seen her once) said that she wanted to run certain tests pre-IVIG b/c my results would never be the same after (these were other tests and nothing to do with the ones from Germany) but how would I know which ones this rule applies to?!!!

This is true, and all your autoantibodies may be affected. If there is an on-going pathological process causing production, they will reappear.

I don't think that getting a clear reading of antibody levels is as important as keeping you breathing. You also have antibodies to GAD65, and I'm hoping those will decline without destroying your ability to produce insulin. Very little has been done in the past to prevent diabetes, and I think we now have a chance. You really don't need that disease added to your troubles.

 

[anciendaze]

Hi @anciendaze interesting post, thanks!

I have hard so far on dysfunctional and agonistic muscarinic receptor antibodies. do you have more information on this destroying issue? Any chances to measure this problem?

Remember that muscarinic acetylcholine receptors are the targets of such things as atropine, found in deadly nightshade, toxins in amanita mushrooms, or the venom of the black mambo snake. I don't know that any autoantibody is that destructive, but I'm not willing to bet this is impossible.

huh?? how come?

They didn't say. I only noticed this when I was searching for new papers on K+ATP channels. The titles were listed, but the text was blocked until the publication embargo is lifted. This is typical of the situation around a major change in a field.

Is this connected to ME/CFS? I don't know.

 

[Gingergrrl]

This is true, and all your autoantibodies may be affected. If there is an on-going pathological process causing production, they will reappear.

So depending on when I do the autoantibody test from Germany in relation to IVIG, in theory it could show I do not have these antibodies when I really do? But that if I do have them, at some point they will regenerate and reappear?

I don't think that getting a clear reading of antibody levels is as important as keeping you breathing. You also have antibodies to GAD65, and I'm hoping those will decline without destroying your ability to produce insulin. Very little has been done in the past to prevent diabetes, and I think we now have a chance. You really don't need that disease added to your troubles.

I agree and I am NOT stopping IVIG and will do RTX 100% if doctor and insurance permit me next year. I was just curious if these treatments (right now just IVIG) could give a false reading on the test and it sounds like they can. I wanted to see both for academic purposes and if having more antibodies might make it easier to get RTX or other treatments in future. But will not be altering my treatment or plans while waiting to do this test and symptom improvement is my #1 goal.

 

[Jemima]

I haven't read the entire thread, but I want to contribute something concerning Gingergrrl's autoantibodies. Every person I have found who tests positive for antibodies to N-type calcium channels has a pretty clear case of POTS. Her response to beta-blockers was also exaggerated, which makes me suspect she has antibodies to beta adrenergic receptors. We'll know when she is finally tested.

Antibodies to either nicotinic acetylcholine receptors or muscle-specific kinase (MuSK) produce the inhibition of neuromuscular junctions seen in myasthenia gravis. Both these are on the post-synaptic side of the junction, and both have purely negative effects, as do antibodies to N-type calcium channels on the presynaptic side.

The jokers in this deal are antibodies to muscarinic acetylcholine receptors, which can do anything from permanently destroying a receptor to causing it to act like it is constantly on. They can also act like reuptake inhibitors, exaggerating the effect of nerve signals the way SSRIs do with serotonin.

Even when restricted to a single neuromuscular junction the problem is quite complicated. Most doctors pretend there is no interaction between various kinds of impairment, an absurdity.

All these antibodies named above have effects that are not restricted to one particular location. I refer to these as "global" actions. There are entire classes of neurotransmitters which are highly restricted in both time and space, and purinergic neurotransmitters (ATP, ADP, AMP) are among them, as is NO. These are very much involved in vasodilation.

The normal response to hypoxia in a muscle or organ is to release such biochemicals so that blood vessels downstream dilate and increase the pressure drop across the organ. This leads to increased blood flow. The timescale for this response is quite short, on the order of the period of a heartbeat. A number of problems where this does not work correctly now appear to involve constant vasodilation, regardless of exercise. You can't dilate something which is already dilated, and you can't increase blood flow relative to other blood vessels if they are already experiencing the same thing.

The confusing thing about this, in terms of medical specializations, is that it doesn't fit any of them. It is not restricted to the nervous system because red blood cells are often the ones that sense local hypoxia and start the signal cascade by dumping ATP. This doesn't show up in measurements of O2sat because the place you are measuring usually does not have hypoxia. It is hard to measure because things like ATP and NO are reactive, and don't persist long enough to be found where it is convenient to draw blood. It does affect large skeletal muscles, but the problem is primarily with capillaries, where it is again hard to measure.

One other thing, we know there are important ion channels which require more than one chemical signal. (One example shows up with NMDA receptors which need both glutamate and glycine. This has been associated with NMDA receptor autoimmune encephalitis, but only the most spectacular cases are currently being identified.) The ion channels we haven't really pinned down are K+ATP channels which involve both potassium and ATP. Everything about these suggests they are important, but there is a great deal we don't know. If this were not so, we would not still be arguing about the very existence of these vital structures. Defects in the way these function have been implicated in everything from diabetes and ischemia/reperfusion injury in the heart, to say nothing of what they do in the brain. A number of papers concerning these are currently under publication embargo until January 2017. Watch for them.

The Musk antibodies are easily tested, Musk disease is a type of myasthenia and there are some treatments people with Musk can try. I have a form of myasthenia from my M,E but not Musk. I have just had a course of ivig over five days.

 

[Jemima]

So depending on when I do the autoantibody test from Germany in relation to IVIG, in theory it could show I do not have these antibodies when I really do? But that if I do have them, at some point they will regenerate and reappear?



I agree and I am NOT stopping IVIG and will do RTX 100% if doctor and insurance permit me next year. I was just curious if these treatments (right now just IVIG) could give a false reading on the test and it sounds like they can. I wanted to see both for academic purposes and if having more antibodies might make it easier to get RTX or other treatments in future. But will not be altering my treatment or plans while waiting to do this test and symptom improvement is my #1 goal.

You could have Musk tested in uk, at Oxford hosiptal and they take tests from the rest of the world i believe.

 

[Jemima]

You could have Musk tested in uk, at Oxford hosiptal and they take tests from the rest of the world i believe.

PS antibody tests would be all over the place on IVIG

 

[Jemima]

Hi @anciendaze interesting post, thanks!

I have hard so far on dysfunctional and agonistic muscarinic receptor antibodies. do you have more information on this destroying issue? Any chances to measure this problem?


huh?? how come?

Yes Musk antibodies can be tested for in uk.

 

[Gingergrrl]

You could have Musk tested in uk, at Oxford hosiptal and they take tests from the rest of the world i believe.

I am not in the UK and was tested for MuSK via Mayo Clinic and was negative. I am going to be attempting to test the autoantibodies from Cell Trend (the tests that Dr. Schiebenbogen developed with them) that are only available in Germany. Myasthenia Gravis and MuSK are ruled out in my case but I do have pretty bad muscle weakness and cannot open my front door (or most doors) or do a leg lift exercise in another thread. Am hoping this improves with IVIG.

 

[Gingergrrl]

Am finally getting to reply to some stuff I missed but still have not had a chance to go back and re-read the whole thread. Thank you to everyone trying to help me for all of your patience!

Have you had standing-laying SpO2 done?

I honestly am not sure. Is this a test performed in a doctor's office? I am wondering if it has another name here? I have had two TTT tests and a QSART (sweat) test done in an autonomic lab and this is also how it was discovered via blood test that I had the N-type calcium channel antibody. The lab test involved deep breathing and valsalva, etc, but I don't remember anything called Sp02 being done.

Spend a tiny bit more money so you get one with nightly recording and export to PC. I bought this one: https://www.amazon.co.uk/Wrist-pulse-oximeter-PULOX-PO-400/dp/B003ITM3WI

I just looked at the watch and Googled the page. I do not have a PC though and am not able to grasp how to use most devices although my husband could help me. What would I be looking for?

The drawbacks are:- does not cooperate with mac, so mac users need parallels

After reading this, it won't work then b/c all of the devices that we own are Macs. I don't know what parallels are. I feel like the village idiot when I respond to these technical posts but am doing so anyway- thanks for baring with me.

That shows just how little I know, as I assumed a vasodilator for the blood vessels in the lungs would help, but you are saying a vasoconstrictor helped.

No worries and in my case, the only medication that ever seemed to be able to bring additional blood to my lungs was Midodrine. However, since having IVIG, I stopped Midodrine and only used it for one day when my systolic BP dropped to 84 and I could immediately feel the difference. But almost every day since IVIG my systolic BP has been over 100, or in the upper 90's, without Midodrine which has been truly bizarre to see but really occurred!

Did you have an SpO2 done?

I still am not sure! Can you explain what it involves or if this test is done by a doctor? I've Googled it but am thinking it must have another name.

Does anyone have further papers to add? Further antibodies that may contribute? I have first written this for myself, but thought, I will post this as part of a bigger list of things on how to test for these receptor antibodies, which antibodies and why.

Thank you so much, Lolinda, for all of the info that you sent me via PM re: Cell Trend and the information that you are compiling. I have not been able to read it all yet and am trying to put it into a format where I can read all of the links. I am confused which tests now to actually ask for b/c my original link to Cell Trend was for three autoantibody blood tests but it appears that they offer many more than that. I am hoping when I finally get to reply to them that they can send me a lab req that I can e-mail to my doctor and choose which tests are most useful in my case.

Every person I have found who tests positive for antibodies to N-type calcium channels has a pretty clear case of POTS.

That is very interesting and I was wondering if you know why? I know the converse is not true in that there are people who have POTS without this antibody so am curious about the mechanism of those like me who have the antibody and POTS. Do you think someday this will be a distinct autoimmune disease with it's own name? Do all of the people that you have come across with the antibody and POTS also have breathing and muscle weakness?

This doesn't show up in measurements of O2sat because the place you are measuring usually does not have hypoxia.

Is the pulse oximeter that measures 02 saturation (which I have at home) the same as the Sp02 test that Lolinda is referring to in her posts above? If so, then I have done this and my pulse ox (measured on finger) is always 97-99% with 2-3 rare exceptions like when I had pulmonary edema in 2014 or a reaction to a medication. But in general it stays at an average of 98%. I can be gasping for air with chest pain, as if I feel like I am about to die, yet the pulse on finger is normal so I know this does not measure what is occurring in my lungs or muscles, etc. I cannot however pass a most basic spirometry test no matter how hard I attempt.

I hope I have not missed any questions asked of me! Please ask me again if I did.

 

[Jemima]

you can have sero negative type of myasthenia, i believe a lot of PWMe do, antibody tests are negative but they have the illness as part of the ME. If you do,well with ivig that ca be a clue. have you ever had a tensilon test for your weakness? Ask your Doctor. But make sure you have it in a hospital,setting incase of reaction. Wha are your other neuro symptoms if you dont mind me asking. Do you ever get low,potassium by the way? I have had two episodes of ecopics with fast heart, this weekend i went to the hospital they did an ekg and said an arrythmia with ectopics but couldnt find a heart reason in particular, but my potassium was 3.3. In UK 3.5 is normal so they sent me home with potassium tablets and this morning nirse came to take a repeat blood tests for potassium. I am really surrised they bothered to treat 3.3 as i have had lower at other times and they didnt bother. I keepmwondering about thyroid but my tests are always ok thyroid wise. I have been in bes for two months this time, the IVIG was five and half weeks ago now. Some things re i proved aome are worse. IVIG can be aroller coaster for a while and then one day it begins to plateau, well in my case anyway. X