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Question re: ANA results

PDXhausted

Senior Member
Messages
258
Location
NW US
@Gingergrrl oh I had one other question for you if you don't mind-- do you find that your symptoms fluctuate at all with your menstrual cycle?

That is one thing that seems weird about me-- I'm bedridden and debilitated all the time but my muscle and brain symptoms are highly correlated with my hormone fluctuations, to the point where I can predict my exact symptoms and ability levels by the day of the month. I was effectively paralyzed while on birth control (used to stop endometriomas from forming).

I cannot figure out if that is a clue to autoimmunity, infection, or some other problem like a genetic detoxification or hormone metabolism problem. None of the 20 or so doctors I've seen so far have any idea. I'm curious if anyone else sees anything like this, even if in a more subtle effect.
 

Gingergrrl

Senior Member
Messages
16,171
@Gingergrrl oh I had one other question for you if you don't mind-- do you find that your symptoms fluctuate at all with your menstrual cycle?

I don't mind and honestly at this point, you guys can ask me anything. Some of my symptoms fluctuate and others do not. My mast cell symptoms/allergic reactions can fluctuate with my cycle and I also get excruciatingly painful period cramps to the point of being curled in a ball sobbing from the pain ready for someone to shoot me to put me out of my misery. Thankfully I have a pain pill for this that works most of the time. But other symptoms like my shortness of breath upon standing etc, do not fluctuate and remain constant.

That is one thing that seems weird about me-- I'm bedridden and debilitated all the time but my muscle and brain symptoms are highly correlated with my hormone fluctuations, to the point where I can predict my exact symptoms and ability levels by the day of the month. I was effectively paralyzed while on birth control (used to stop endometriomas from forming).

I learned from fertility specialists that I was unable to get pregnant so have not needed to use birth control in many years. I suspect if I had used the pill that I would have gotten horrible side effects. Doctors have said I do not have endometriosis in spite of the severity of the cramps that I've had since age 13.

I cannot figure out if that is a clue to autoimmunity, infection, or some other problem like a genetic detoxification or hormone metabolism problem. None of the 20 or so doctors I've seen so far have any idea. I'm curious if anyone else sees anything like this, even if in a more subtle effect.

I wish I knew but sadly have no expertise in this area!
 

PDXhausted

Senior Member
Messages
258
Location
NW US
Thanks @Gingergrrl ! Surprisingly, despite having severe endometriosis (at one point I had 1.5 liters of blood in my cysts in my abdomen) I don't really have severe pain or cramps, except the times where the cysts have ruptured. Just goes to show that gyn disease is probably more nuanced than anyone is willing to research.

Although now I'm wondering if calcium channels are involved in menstrual cramps somehow and maybe that might explain your pain. I think estrogen has something to do with calcium metabolism- at least in regard to bone density.

And just a general comment- not necessarily toward you but in case anyone else comes across this thread that has experienced this-- I've wondered if maybe I could have elevated anti-NMDA antibodies which I know can be associated with terratomas, but doctors always brush me off when I ask to be tested, I think due to lack of acute disease and lack of terratoma.

Ostensibly I don't have a terratoma, but I've wondered if it was possible to have a couple cells of a terratoma that could cause a mild increase in antibodies and a more mild or chronic form of disease.

Anyway, if I can manage to get my blood drawn for the Mayo panel, I'll know eventually.
 

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
@kangaSue my husband just found a research article from 2015 NIH website (that I have not read yet but will soon) which says that the frequency of n-type and other VGCC calcium channel Abs is 2.3 per million people!!! I am shocked at this statistic!

ETA: Here is the link to the article:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360501/
We all strive to be a member of an exclusive club, don't we? :)

The statistic quoted in the paper is only in relation to LEMS occurring in the general population though where P/Q-type VGCC is the dominant antibody finding whereas N-type VGCC is less found in LEMS but is a more prevalent finding in a range of other autoimmune conditions so you will find you have more buddies in the club than first realized.
 

Gingergrrl

Senior Member
Messages
16,171
We all strive to be a member of an exclusive club, don't we? :)

The statistic quoted in the paper is only in relation to LEMS occurring in the general population though where P/Q-type VGCC is the dominant antibody finding whereas N-type VGCC is less found in LEMS but is a more prevalent finding in a range of other autoimmune conditions so you will find you have more buddies in the club than first realized.

I quoted it based on my husband's interpretation prior to seeing the article and after reading it myself, I read it exactly as you did which was a bit of a relief. So LEMS is 2.3 per million but the VCGG (ETA: N-type) antibodies are more common. I was stunned when I thought that it was that rare and glad it is not! Either way, this is a club that I would like to un-join LOL.
 
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Gingergrrl

Senior Member
Messages
16,171
Thanks @Gingergrrl ! Surprisingly, despite having severe endometriosis (at one point I had 1.5 liters of blood in my cysts in my abdomen) I don't really have severe pain or cramps, except the times where the cysts have ruptured. Just goes to show that gyn disease is probably more nuanced than anyone is willing to research.

Am glad you do not get the severe cramps but am sorry about the cysts and it all sucks IMO.

Although now I'm wondering if calcium channels are involved in menstrual cramps somehow and maybe that might explain your pain. I think estrogen has something to do with calcium metabolism- at least in regard to bone density.

I know that prostaglandins and MCAS are related to it but am not sure about the rest. I really wish I had studied science in school back when I had the opportunity.

And just a general comment- not necessarily toward you but in case anyone else comes across this thread that has experienced this-- I've wondered if maybe I could have elevated anti-NMDA antibodies which I know can be associated with terratomas, but doctors always brush me off when I ask to be tested, I think due to lack of acute disease and lack of terratoma.

There is a very good book called "The girl on the 6th floor" which is a true story written by the girl's father re: her ordeal with having the anti-NMDA antibodies. She had seizures and psychosis and symptoms that I have not had but once they finally discovered what was happening (via the Mayo testing) she was treated with IVIG and Ritiuximab and made a very good recovery. Otherwise, she would have died.

I do not read fast but read this book really quickly b/c it was so interesting to me. They tested her over and over for ovarian cancer but never found anything. They concluded that if she had a few cancerous cells, the body got rid of them on it's own and then she developed the paraneoplastic syndrome.

For me, it was also interesting that regardless of which antibody, the treatment seems to be IVIG and RTX which is why I am so determined to do both and am finally doing the first one now.

Ostensibly I don't have a terratoma, but I've wondered if it was possible to have a couple cells of a terratoma that could cause a mild increase in antibodies and a more mild or chronic form of disease. Anyway, if I can manage to get my blood drawn for the Mayo panel, I'll know eventually.

After reading that book, I think it is very possible that you could have had (or still have) a few cells which are causing an increase in the antibodies. What brain related symptoms do you have? If I were you, I would really fight like hell to get that test. I was not tested for the NMDA test b/c I had no brain related symptoms vs. severe dysautonomia, muscle weakness and breathing symptoms.
 

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
I quoted it based on my husband's interpretation prior to seeing the article and after reading it myself, I read it exactly as you did which was a bit of a relief. So LEMS is 2.3 per million but the VCGG antibodies are more common. I was stunned when I thought that it was that rare and glad it is not! Either way, this is a club that I would like to un-join LOL.
Ah, husbands eh. Can't live with them, can't live without them.
Your lucky, I'm only a half member with all the encumbrances but don't qualify for the perks like IVIG :)
 

Gingergrrl

Senior Member
Messages
16,171
but don't qualify for the perks like IVIG :)

Sorry if this is a stupid question but would IVIG help your GI diagnosis and did you ever learn if you were positive for AAG? I know IVIG is the treatment for AAG but wasn't sure if you ever got confirmation of that. If IVIG is the treatment, can you fight for it like I did or is there no chance of getting it in Australia? I was flat-out turned down by three doctors and just kept trying until I found a Neuro willing to take a chance on me and her backing allowed my main doc to put in the referral to my insurance and convince my local doc to administer it. It took me five months of advocating to make it happen and was definitely ready to give up at moments. I really hope that you can get it somehow if it is the treatment that you need and @PDXhausted, too.
 

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
Sorry if this is a stupid question but would IVIG help your GI diagnosis and did you ever learn if you were positive for AAG? I know IVIG is the treatment for AAG but wasn't sure if you ever got confirmation of that. If IVIG is the treatment, can you fight for it like I did or is there no chance of getting it in Australia? I was flat-out turned down by three doctors and just kept trying until I found a Neuro willing to take a chance on me and her backing allowed my main doc to put in the referral to my insurance and convince my local doc to administer it. It took me five months of advocating to make it happen and was definitely ready to give up at moments. I really hope that you can get it somehow if it is the treatment that you need and @PDXhausted, too.
I tested negative to ganglionic AChR Ab. 50% of cases are negative but in those with a (Restricted) Autonomic Neuropathy diagnosis, IVIG has been found to be effective in some of those considered idiopathic rather than autoimmune.

I thought that if it came down to it, I could just pay for IVIG treatment out of pocket but supply of IVIG is covered by Government regulation and you have to get approval for it's use through a hospital if it's use falls outside the specific conditions that are fully subsidised under our Medicare provisions.

I needed to have a positive antibody finding to qualify for IVIG, my N-type VGCC level being considered negative as it is in the "normal range", go figure.

I have found one last avenue to explore. I wasn't antibody tested other than ANA panel when I had a cancer diagnosed in 2009 but donated blood to a research study before and after the cancer was removed and it's looking like I can still get the "before" sample tested for N-type VGCC. It would be somewhat atypical but if the cancer was a paraneoplastic cause, removing it can completely eliminate of just reduce the titre of circulating antibody in some people so my last chance for getting IVIG is that the stored blood tests positive to N-type VGCC.

Just waiting to hear back from the head scientist of the study to see what bureaucratic hoops I have to jump through to have some blood released to me.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards This seems strange to me b/c a doctor tested me for the paraneoplastic panel, discovered I had the N-type calcium channel antibody, and then that I had a positive ANA 1:160 speckled pattern (when all prior ANA's were negative.)

There must be a connection b/c this antibody blocks calcium from going into the cells and there is now research that shows when athletes exercise, they can leak calcium from the cells. So whether it is leaking or being blocked by an antibody, the calcium is not inside of the cell and it can cause muscle weakness, pain, and all sorts of problems. It seems like scientists would be interested in the more obscure antibodies, especially when someone who has them are so sick.

If they highly correlate to small cell lung cancer and LEMS (Lambert Eaton Syndrome) then they are capable of causing severe damage. It seems like treating or reducing them at at earlier point would be of value (to the patient and to furthering science.) All I was told is to get a high resolution lung cat scan every six months and to get tested for LEMS which I did immediately. I had to fight like hell to get IVIG (which I am doing now) and every step of this process is occurring b/c I have found solid doctors to help me and an iron-clad will to keep going.

It seems like science saying, "We don't know and we don't care" is a cop-out and like @Strawberry I am just venting and this is not directed at you or any one person!

We don't know and we don't care are quite different things, Gingergrrl.

The very best neuroimmunologists in the world have been looking hard for autoantibodies that might interact with nerve or muscle and they have found noting in PWME different from normals so far. Some f the very best people are actively looking at ME/CFS. You do not hear much because nothing has been found.

The problem with linking autoantibodies to calcium flux in ME/CFS is that it would not seem to add up to any story that makes sense on the basis of what we have already researched. In Lambert Eaton syndrome there is a specific type of 'myasthenia' that is quite unlike ME/CFS. The muscles of PWME have been studied in detail in MR spectroscopy and from what has been published it looks as if they are pretty normal chemically. I guess that suggests that if you have calcium channel antibodies and weakness you probably have an illness that is quite different from the great majority of people who are diagnosed with ME. The idea that these antibodies might be a common cause of ME does not seem to add up. (In small cell lung cancer it is the cancer that causes the antibodies, not the other way around.)

I quite agree that it would be good to have more scientists working on ME. But when it comes to this sort of neuroimmunology it is not so much that we are short of scientists than that the scientists are short of ideas on what to look for next since they keep finding nothing they can link up to form an explanation.
 

Gingergrrl

Senior Member
Messages
16,171
I guess that suggests that if you have calcium channel antibodies and weakness you probably have an illness that is quite different from the great majority of people who are diagnosed with ME.

This is what I am trying to express. I have no idea (truly) if I actually have ME or a different illness. I have a proven autoantibody and proven positive ANA titer by testing plus muscle weakness, lung and breathing weakness, dysautonomia, POTS, etc, but science is not interested in studying this and traditional medicine dismissed me and there was never mention of the words ME or CFS to any of these doctors. So from my perspective not knowing equaled not caring. The doctors who are helping me are the angels and mavericks who are willing to look and think outside of the box.
 

Gingergrrl

Senior Member
Messages
16,171
The very best neuroimmunologists in the world have been looking hard for autoantibodies that might interact with nerve or muscle and they have found noting in PWME different from normals so far.

Sorry this is in a separate box and my phone not letting me add more quotes to my first post. I was curious if the neuroimmunologists who are looking hard at these autoantibodies to see if they interact with nerves or muscles are finding leads at all (even in people who do not have ME/CFS) and if this topic is actually being researched or studied (vs. if they are finding differences in those with ME/CFS and without it). I think they first need to study the autoantibodies in general just to gather some info which seems to be being done at the Charite in Germany but am not aware of anyone in the US? But would love to be wrong!

(In small cell lung cancer it is the cancer that causes the antibodies, not the other way around.)

This is also confusing to me b/c the doctors said you can have the antibodies first and the cancer (SCLC) can appear 3-5 years later, or it can never appear if your immune system wiped it out at the point of it only being a few cells. Or in some cases, you have the antibody but you never had or will ever have the cancer. Can you explain this part? It is very confusing to me.
 

Gingergrrl

Senior Member
Messages
16,171
@kangaSue wow, that is insane what they are putting you through to try IVIG and I am crossing all fingers and toes that your prior research sample allows you to get what you need. We have similar beauracratic hoops here with the insurance companies although different content and process.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Sorry this is in a separate box and my phone not letting me add more quotes to my first post. I was curious if the neuroimmunologists who are looking hard at these autoantibodies to see if they interact with nerves or muscles are finding leads at all (even in people who do not have ME/CFS) and if this topic is actually being researched or studied (vs. if they are finding differences in those with ME/CFS and without it). I think they first need to study the autoantibodies in general just to gather some info which seems to be being done at the Charite in Germany but am not aware of anyone in the US? But would love to be wrong!

Te neuroimmuiologists include those in Oxford. I would be pretty sure there are others in the US. The potential interactions with nerve and muscle are part of major research programmes, but not linked to ME/CFS because nobody has found much in ME/CFS. Note that although the Charité study shows a drop in antibody after rituximab it is not clear that there are more antibodies in ME/CFS patients than normals so they may not have anything to do with the illness. (All autoantibodies tend to go down after rituximab anyway.)


This is also confusing to me b/c the doctors said you can have the antibodies first and the cancer (SCLC) can appear 3-5 years later, or it can never appear if your immune system wiped it out at the point of it only being a few cells. Or in some cases, you have the antibody but you never had or will ever have the cancer. Can you explain this part? It is very confusing to me.

The cancer may take five years to appear on scan after causing the antibodies because very small cancers can stimulate the immune system to make autoantibodies and most cancers grow very slowly for their first five years. The cancer is there first. If it is a benign or very slow growing tumour it may never grow big enough to see. But the autoantibodies can be made by chance without a cancer as well. The same situation occurs with anti-sdnthetase antibodies and dermatomyositis. A significant minority of people have a cancer causing the antibodies, which may go away if the cancer is removed, but others just have the antibodies.

What I am pretty certain of is that nobody has ever suggested that the antibodies cause cancers. If they did you would expect some people with the antibodies to get more than one lung cancer and that is not seen. It is more or less impossible for antibodies to cause cancer because cancer is due to a complex series of changes in the cell nuclear DNA - which antibodies have no way of changing.
 

Strawberry

Senior Member
Messages
2,107
Location
Seattle, WA USA
get excruciatingly painful period cramps to the point of being curled in a ball sobbing from the pain ready for someone to shoot me to put me out of my misery. Thankfully I have a pain pill for this that works most of the time.

You just explained my daughter! What is the pill that works for you? Pretty please? :angel:
 

Gingergrrl

Senior Member
Messages
16,171
Te neuroimmuiologists include those in Oxford. I would be pretty sure there are others in the US. The potential interactions with nerve and muscle are part of major research programmes, but not linked to ME/CFS because nobody has found much in ME/CFS. Note that although the Charité study shows a drop in antibody after rituximab it is not clear that there are more antibodies in ME/CFS patients than normals so they may not have anything to do with the illness. (All autoantibodies tend to go down after rituximab anyway.)

@Jonathan Edwards Thanks, Dr. Edwards, and I know of Dr. Angela Vincent in the UK but there really does not seem to be neuro-immunologists (or any doctors) focused on these auto-antibodies or channelopathies in the US (or if so, they are hidding!) I do not know to what degree my symptoms are caused by the calcium antibody but would love to learn more about the interaction between the antibody and the nerves/muscles as you mentioned. I have no idea if they correlate higher in someone with ME/CFS (nor am I certain that ME/CFS is my diagnosis as much as I would like to know for sure).

But I wish there were a scientist or researcher who knew how to tie this all together b/c I have too many different symptoms/abnormalities on tests for them all to be a coincidence and I can't believe that what I have is rare to really just be a few cases per million people. Maybe all the people with positive ANA's who are negative for the well-known diseases like RA and Lupus, actually have these more rare auto-antibodies but are just not being tested.

I have had some minimal improvement from one treatment of IVIG so can only imagine (if my insurance permits me to continue the infusions and to raise the dose and to later try RTX), how much improvement I could have in theory. I feel like I'd be a great research case if anyone were interested and I'd be willing to be a guinea pig.

The cancer may take five years to appear on scan after causing the antibodies because very small cancers can stimulate the immune system to make autoantibodies and most cancers grow very slowly for their first five years. The cancer is there first. If it is a benign or very slow growing tumour it may never grow big enough to see. But the autoantibodies can be made by chance without a cancer as well. The same situation occurs with anti-sdnthetase antibodies and dermatomyositis. A significant minority of people have a cancer causing the antibodies, which may go away if the cancer is removed, but others just have the antibodies.

This still confuses me and different doctors have expressed different opinions re: the antibodies and paraneoplastic syndromes. For my antibody (N-type VGCC Ab) the correlated cancer is small cell lung cancer. My doctors have said that this is a very fast growing aggressive cancer that would kill you if not discovered early (and probably kill you any way) and would never be a slow growing cancer that takes five years to discover. So it would seem that I have the autoantibody in the absence of cancer *or* that the antibody is here first and the cancer will come later (or there will never be cancer and I just have the antibody.) But in the case of SCLC, it doesn't make sense to me how it could come first and slowly grow for five years before discovery?

What I am pretty certain of is that nobody has ever suggested that the antibodies cause cancers. If they did you would expect some people with the antibodies to get more than one lung cancer and that is not seen. It is more or less impossible for antibodies to cause cancer because cancer is due to a complex series of changes in the cell nuclear DNA - which antibodies have no way of changing.

I agree the antibody does not cause the cancer but was told that different autoantibodies correlate with different types of cancers. Some doctors have expressed to me that knocking down the antibody now (through IVIG, RTX, plasmapheresis if it were available, etc) reduces my chance of getting cancer in the future while others have disagreed and even expressed that the antibody serves some kind of protective factor to fight the cancer from growing beyond a few cells. The level of contradiction/confusion amongst smart doctors seems strange to me but I guess the paraneoplastic syndromes are not well understood or studied?

I am certain there must be some connection with auto-antibodies and ME/CFS, at least in one sub-group, or else meds like RTX would not help those individuals?
 

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
This still confuses me and different doctors have expressed different opinions re: the antibodies and paraneoplastic syndromes. For my antibody (N-type VGCC Ab) the correlated cancer is small cell lung cancer. My doctors have said that this is a very fast growing aggressive cancer that would kill you if not discovered early (and probably kill you any way) and would never be a slow growing cancer that takes five years to discover. So it would seem that I have the autoantibody in the absence of cancer *or* that the antibody is here first and the cancer will come later (or there will never be cancer and I just have the antibody.) But in the case of SCLC, it doesn't make sense to me how it could come first and slowly grow for five years before discovery?
Just want to point out that, while it's widely reported in the medical literature that lung cancer as a paraneoplastic syndrome will invariably be small cell lung cancer, this is an incorrect assumption by even Specialists and there is a small percentage of people who also get large cell carcinoma as a paraneoplastic syndrome.
 

Gingergrrl

Senior Member
Messages
16,171
You just explained my daughter! What is the pill that works for you? Pretty please? :angel:

Am sorry that your daughter experiences this, too, and I take Norco 5/325. I take 1/2 pill but for severe cramps I take a whole pill. I have a dye-free version b/c of my MCAS but if this is not relevant for your daughter, will spare you the extra details!