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http://mastcelldisorders.wallack.us/yabb/YaBB.pl General Mast Cell Disorders Discussion >> General Mast Cell Disorder Discussion >> please help me understand tryptase testing http://mastcelldisorders.wallack.us/yabb/YaBB.pl?num=1399550404 Message started by Kalle on 05/08/14 at 01:00:04

Title: please help me understand tryptase testing
Post by Kalle on 05/08/14 at 01:00:04

I will be asking my internist to do a serum tryptase test for me but I've read that unless we are having a reaction at that time the test will probably be normal even if we have MCAD. I'm not willing to take a drug or eat a food that I know will cause me a serious reaction just to get a correct test. What is the point of taking the test? Thanks.

Title: Re: please help me understand tryptase testing
Post by Bruce Hart on 05/08/14 at 05:20:18

Hi Kalle. If you're wanting to be tested for MCAD I would ask a local doctor if they would be willing to consult with Dr. Afrin, who is happy to consult with people's local doctors. He's my favorite MCAD specialist, based on publications. Because even if you can get a local doctor to do the tests, the doctor would not know how to interpret them, so you really need a doctor knowledgeable and experienced with MCAS to interpret the tests and decide what to do next, and the best treatments to try.

Yeah for MCAS, mast cell mediators, including tryptase, are often not elevated unless samples are taken during, or soon after, a substantial flare of symptoms, but tryptase elevated at baseline is an indicator of systemic mastocytosis (SM), and is often used to justify a bone marrow biopsy to confirm or disconfirm SM. And tryptase > 20 ng/mL is also a minor criteria for SM, so can help make the diagnosis, but tryptase is below 20 ng/mL in 20% of cases of indolent SM. "Increase in serum total tryptase of 20% above baseline plus 2 ng/mL during or within 4 h after a symptomatic period" is one of the proposed criteria of MCAS. But elevation of other mast cell mediators are also tested and it varies per MCAS case which mediators are elevated, but with current tests, normal levels of mast cell mediators can not rule out MCAS.

I can relate about not wanting to purposely have a strong reaction to something for it to show up on tests since that could chronically worsen my sensitivity. The solution is to wait until you accidentally have a strong reaction and then start urinating in a jug for a 24 hr urine test for PGD2 and N-methylhistamine. And get a doctor note for emergency room (ER) to draw blood samples for tryptase, chromogranin A, and histamine soon after you have a strong reaction. Many of the test samples need to be chilled at all times, during collection and transport.

Although, it can be a challenge to get ER to draw blood for the tests.

Dr. Afrin:

"those who do travel to an urgent care facility or emergency department often encounter providers resistant to pursuing tests not needed for immediate care of the presenting symptoms."

For more info on testing and criteria see:

http://www.wjgnet.com/2218-6204/pdf/v3/i1/1.pdf

Title: Re: please help me understand tryptase testing
Post by Kalle on 05/08/14 at 10:34:13

Thanks for your info. My internist ordered the tryptase test but did not have a code for histamine so I can forget about that. The nurse didn't draw the correct amount of blood so I have to go back to dr's office & give more blood. I'm in a small town & it would not only be a challenge to get hospital to draw blood it would probably be impossible. My dr didn't know about MCAD but he was willing to look up the info he needed in spite of it interfering with his busy schedule. I am thankful for that. I know the hospital staff would not know what I was talking about. I will discuss your suggestion with my dr. he seems willing to help. thanks again!

Title: Re: please help me understand tryptase testing
Post by Bruce Hart on 05/08/14 at 12:18:17

Hey Kalle, that's great you have a nice local doctor willing to try. It sounds promising he may learn about MCAD, so later if he seems to become familiar enough with MCAD testing, including MCAS, then I hope you will mention him in the MCAD Doctors section on this forum to help others near you.

Title: Re: please help me understand tryptase testing
Post by Lisa on 05/13/14 at 16:50:45

Hi Kalle,

Tryptase is more important to get at a baseline than it is as an acute marker. Why? Because it is at baseline, when you are not in a crisis event, that the real picture of what is going on with you is revealed. Several baselines are good to see exactly whether you may have mastocytosis or MCAS.

Tryptase shows what the MC burden is within your bone marrow. This is why it is low in MCAS patients. However, a low baseline of trytpase does NOT rule out MCAS and this is why they test for other mediators as well like histamine and prostaglandins.

Bruce is right, they will use this to judge whether or not a BMB is necessary but there are times they will ask for a BMB even if the baseline is low. I've had one already and my baseline is 4.6ng. And when I went into anaphylaxis back in September due to a local injection of lidocaine my crisis tryptase was 4.0ng, below my baseline!!!

What does that mean? Well, in an IgE allergic reaction the tryptase will almost always become elevated, but in mastocytosis, because the degranulation is selective, trytpase is not always the major mediator being released. There are other mediators which are even more potent than tryptase and they will create anaphylaxis on their own and in very small quantities. This is why tryptase is not always reliable as proof of MC activation. Yet, again, it is reliable as a means of knowing what the MC burden is and an accurate exam for diagnosing systemic mastocytosis.

I hope that helps!

Lisa

Title: Re: please help me understand tryptase testing
Post by peter on 05/13/14 at 20:04:42

Ha Lisa is the massive increase in tryptase in IgE anaphylaxis A massive increase in mast cells and how could that happen so Quick

Also what course chronic increasing tryptase

Title: Re: please help me understand tryptase testing
Post by Lisa on 05/15/14 at 03:14:43

Hi Peter!

As you know we need our MCs to defend our bodies. Well some of us have real allergies. When we do then we also have antibodies. Every time we are introduced to an allergen, then more antibodies are created. The more, the merrier, huh?! The more we have, then the more MCs are triggered and the bigger the reaction gets.

When an MC is triggered by real allergies then the IgE receptor is triggered and the entire MC explodes with ALL of the mediators spilling out.

Yet, in masto the mechanism is totally different. The MC is selective in it's ability to release mediators and because the Kit membrane which surrounds the MC is defective it means that not only do you NOT need a receptor for the mediator to be released but the MC is also able to choose which mediator it wants to release. The cell is not distroyed as it is in a true IgE explosion. The cell remains whole and full of other mediators which it chose not to release for whatever reason.

So, in an IgE mediated allergy, the MC releases EVERYTHING it's got and tryptase included. This is why the tryptase test is important to confirm anaphylaxis but is useless to diagnose MCAS. Why? Because when you have an IgE mediated allergy and go into anaphylaxis the chances are you've got a WHOLE BUNCH OF MCs BEING DESTROYED AND DUMPING ALL OF THEIR MEDIATORS AT ONE TIME!

Yet, in anaphylaxis caused in masto the MCs are not massively destroyed. Although some of the normal MCs will join in the fun, the major MCs being triggered are really only those which are malfunctioning. And when they trigger then they SELECTIVELY RELEASE their CHOSEN mediators and tryptase may not be one of them.

Is the patient in anaphylaxis in a masto related crisis? YES! Why? Because anaphylaxis is not dependant upon any single mediator and that's never been studied before, so nobody is really looking at which mediator is at fault and they've been able to show that there are several specific mediators which can cause anaphylaxis - histamine, Platelet Activating Factor and a few others which are extremely potent mediators. Yet they measure Tryptase because they have found that in IgE anaphylaxis it is always present and in large quantities.

In fact, I rather think that the authorities are beginning to abandon the idea of asking for trytpase in crisis mainly because of the contradiction which we patient present. When they found that tryptase was an important mediator which proved anaphylaxis they didn't know at that time that the MC was capable of selectively releasing its mediators - this is a pretty recent finding. So, in the fact that we masto patients go into anaphylaxis, it's very curious that in some of us our tryptase will NOT elevate above our baselines. It means that they need to find a mediator which will consistently rise and use this as the way to judge masto patient's and their crisis events. Another reason why tryptase in crisis is not useful in us is because of their recently finding that other mediators are extremely potent, even more than histamine, in causing anaphylaxis! It means that the anaphylaxis event is not caused by tryptase but by other mediators, which they still don't know exactly.

So, how is anaphylaxis judged? By the symptoms and this is what causes such confusion for our doctors for they aren't taught any other way of recognizing it except by IgE mediated anaphylaxis - the total explosion result.

Yet in masto patients our reactions are a result of what mediators the defective MC chose to release and in what quantities those mediators were in and also as to our genetics and even form of masto we have! This is why we can present anaphylaxis as merely as a crisis of diarrhea, flushing and hypotension or we can show it by flushing and hypotension, or edema and hypertension, etc. It can be isolated to certain systems instead of a total system envolvement.

So, this should help you understand why in IgE the elevation can be massive and then quickly reducing back to normal levels once the reaction is over. The number of MCs themselves do not increase, Peter. They should actually be reduced in number which the body would then normalize to it's normal amount of MCs. In people who are allergic, they have normal numbers of MCs. In mastocytosis is when you have increased numbers.

Title: Re: please help me understand tryptase testing
Post by peter on 05/15/14 at 19:10:43

I see so ige anaphylaxis with clonal mast cells Thay don't die but get Damage then infiltrate the bone marrow witch courses the increasing Tryptase without anaphylaxis

Title: Re: please help me understand tryptase testing
Post by Lisa on 05/16/14 at 02:25:35

EXACTLY PETER!!!!!

The baseline trytpase is nothing more than a measure of the "burden" of mast cells within the bone marrow and other tissues. They are constantly releasing trytpase - chronic release. But the more there are, the more tryptase goes up on a constant, chronic basis.

Anaphylaixis, especially IgE allergy mediated anaphylaxis, will jack it up in a quick peak as an "acute" reaction but then will drop very quickly back down to it's baseline.

So, this is why baseline tryptase is much more important than the crisis tryptase. Crisis trytpase merely confirms anaphylaxis but does not confirm mastocytosis. Baseline tryptase confirms mastocytosisis and since tryptase is known to come only from mast cells it then is also a confirmation of MC Activation.

Understand?

Lisa

Title: Re: please help me understand tryptase testing
Post by peter on 05/16/14 at 12:45:12

That explains how constant IgE activation damage mast cells
Then the damage cells accumulat to forum tumors or sarcoma
When a few damaged mast cells get into the bone marrow the immune system response to Kill the damage cells in the bone marrow also Kills the sarcoma

That all immune response is what course the symptoms and exstream body Hypersensitivity it's the timing of when the IgE damage mast cells enter the bone marrow and the number that make the differenc
Thanks Lisa

Title: Re: please help me understand tryptase testing
Post by Lisa on 05/21/14 at 17:32:22

Hi Peter,

I'm confused. I didn't say that the constant IgE activation damages the MCs as in that's what's behind mastocytosis. It's not this at all.

In mastocytosis there is a genetic defect on all of the MCs. In fact, they have proven that there is more than one genetic defect. This defect is on the membrane which lies around the cell itself. This make is very vulnerable and easily triggered. The MC doesn't need to be triggered through IgE and often IgE isn't even involved, so in that sense what you are saying about constant IgE activation has nothing to do with this. In fact, what you have said about "constant IgE activation" is nothing more than someone with chronic true allergies. There are loads of people who live with true allergies but they never go on to get tumors or sarcoma ou even mastocytosis due to the constant IgE activation.

You see, Peter, when the mast cell is activated by IgE it's compelely destroyed - it can't regenerate and then the dead cell ends up being filtered out of the blood along with many other dead blood cells. This is normal body function.

Mastocytosis is a disease where the cell itself is formed with the genetic defect from the time it develops from the progenitor cell. Again, depending upon the defect, if it has the one which has been found with SM, then the MCs will aggregate and form small "tumors" as you said. Yet, these are not cancerous and they do not form into a sarcoma. Sarcomas are made up of other cells I believe and not mast cells. The only real MC tumor is called a mastocytoma.

As to the accumulation of the MCs going into the bone marrow, it's also not quite like this.

MCs are called to go into tissues where they go to help support blood vessel growth and health, they go into tissues like the mucus membranes in the nose, throat, intestines, etc, wherever there is tissue which is exposed to the outside world in some form. They remain there and when they have the SM defect on those cells, they then will accumulate one after another and invade the tissues through proliferation of these very same cells. They end up crowding out other cells. It's NOT like a true cancer where the cells divide themselves. Instead it's more like a party where you go people who crash the party and invade adding more partygoers to the original list. They are uninvited and end up forming a crowd.

This is why mastocytosis is not really considered a cancer - the cells don't divide and multiply and mestastize. They are born in a normal blood process only the defective ones just don't die off and they end up forming clumps which then eventually crowd out the other cells.

They end up migrating to the bone marrow because some are formed there and they don't exactly migrate there but they end up not leaving there, I believe. So they stay in the marrow where they should not be and thus they begin to crowd out the other cells which should be there. It's like filling a sausage case with the meat, it eventually takes over depending upon the form of masto you have.

As to the second part of your comment, Peter, this too isn't quite like this.

According to the research, and I've been talking with Dr. Escribano about some of this, they honestly can't seem to find MC aggregates in the non-clonal masto patient. This is why they call them "non-clonal". However, they know that there is some kind of clonality going on in that you have patients who have damaged MCs and that those damaged MCs are activating without clumping together. In finding more than one genetic defect on the MCs, they have found that this explains the activation and the fact that those cells don't aggregate. So, if you have a patient with MCAS who does not have the activation defect, you can't say that their MCs are entering into the bone marrow. In fact, they really don't understand yet how it is that the MCAS patients can be as reactive and even more so than the SM patients. And they can't explain why there are patients who have ASM - aggressive masto, and that they are not as reactive at times as those patients who have the non-clonal form!!! They can't explain it yet, they just don't know! So, you can't say that they hypersensitivity begins upon the MCs entering the bone marrow. Why? Because there are plenty of us who have undergone BMBs and almost no MCs can be found in the marrow and zero aggregates!

It's still a big mystery still Peter and a really hard nut to crack!!!!

I hope this helps you to understand!

Lisa

Title: Re: please help me understand tryptase testing
Post by Joan on 05/21/14 at 18:47:03

My understanding is that the mast cells in SM do die off, but it takes a much longer time than with normal mast cells, so there are too many because they're not dying off fast enough. Is that what you 've read, too?

Title: Re: please help me understand tryptase testing
Post by peter on 05/21/14 at 19:46:28

Yes Joan that was my experience the only way it could have happen with my
Isolated bone marrow mastocytosis
The 6 mast cells that got into the bone marrow did die it took a few years
And chronic increasing Tryptase for 12 months but there gone as my tryptase was slowly coming down arfter venom anaphylaxis for 12 months before The only thing that could have caused the chronic increasing Tryptase was the BMB The only way that could happen is if the few mast cells got into the bone marrow at that time
Lisa you have definitely confused me if mast cells are damage then the immune system don't work properly opening the window for disesse or tumors we don't know what type of tumor was on my chests because it disappeared to weeks arfter it appeared the same week as the BMB
What else could do that

Tryptase 200 then 41 then 31 then BMB 40 ; 50 ; 60 ; 65 Zometa 60 ; 50 ; 40 ; 30 ; 25
BMB no mast cells

Title: Re: please help me understand tryptase testing
Post by Joan on 05/22/14 at 17:08:53

Do you think the Zometa had anything to do with lowering tryptase?

Title: Re: please help me understand tryptase testing
Post by peter on 05/22/14 at 18:39:05

I think the Zometa helped stop the tryptase from increasing and treated what was complications from chronic clonal mast cell activation but the mast cells died from old age
The exstream hypersensitivity is the most disabling but it is also how I New what was happening in my body I could feel everything I had pain from osteoporosis witch is pain less I can tell you there is a hell oF a lot happening in the body that we never know about but with hypersensitivity you feel it all that has come back to normal well a normal level for me

If the research has found a way to kill cancer by a few mast cells in the bone marrow then it's been worth it some of the best things are found by accident

Title: Re: please help me understand tryptase testing
Post by peter on 05/22/14 at 18:52:13

Joan when I had a brake with Zometa the tryptase started going back up when I went back on Zometa the tryptase stopped going up but it might have been treating the leftover cancer cells from the tumor we don't know how all this work's but I do know What happened

Title: Re: please help me understand tryptase testing
Post by Lisa on 05/23/14 at 10:04:47

Peter, there's a difference between the mast cells which are genetically damaged by the defect for mastocytosis and those mast cells which are completely normal. IgE release destroys mast cells - it doesn't "damage" them.

This is what I'm saying. When you have chronic IgE activation you are not damaging any MCs. A normal, functioning, healthy MC ends up exploding to smithereens when it is triggered by IgE. So, it can't go on to doing anything else - it's totally destroyed.

In mastocytosis the MCs when they trigger by anything other than IgE only degranulate and then recompose the granules. They aren't destroyed and since they are already damaged the triggering doesn't do any extra damage. It's already damaged.

Something I didn't know but one of my doctors told me is that when you have any kind of a disease like masto, one that works around neoplasms, there is always a higher risk to having other neoplastic diseases. In mastocytosis there is a higher risk due to the presence of the defect.

MCs like all other white blood cells come from a singular mother- progenitor cell (Jilly Bean is the one to really teach this because I still don't understand it all). This progenitor cell has programed within it the capacity to modify and change into the cell that it's meant to be. Somewhere along the line is where the defect comes it so that by the time it forms into a MC, then it is born defective and remains so. It doesn't die off as soon as it is supposed to and thus begins clumping together and then forming "tumors" which are not in that sense a "true tumor" for the cell itself doesn't divide and multiply, it only sticks together with like company. So, it forms a pseudo-tumor and even though it's called a "neoplasm" it's not a true neoplasm. And normal it's so very slow growing accumulation that it's not an aggressive situation in the least.

It's like a band of tumor "wanna-be's" in that these defective MCs have a magnet or are lined with velcro and they stick together in clumps and form sheets of these cells. In forming these clumps they end up pushing out of the way the normal, healthy cells which should be in their place. When this happens within the tissues, this is where it gets a "tumor-like" behavior for the body needs those normal cells to be present but the block party turns into a mad, caotic riot of MCs and this makes it so that the tissues and organs fail due to that damage.

Tryptase is usally reflective of this invasive damage and behavior - the proliferation and accumulation of these defective MCs. According to the researchers the tryptase levels are pretty acurate in showing the MC burden within the bone marrow. It would be chronically raised because you have a lot of MCs in the bone marrow. The higher the number of MCs the higher the baseline trytpase.

So, if your tryptase is lowering, then that means that the MC burden is lowering too. Yes, defective MCs do eventually die off, but if it disappears I don't know. According to the research it's a progressive kind of thing but extremely slowly progressive. But I can stabilize. Whether it reduces the literature doesn't state.

However, one thing I've notice in the years I've been on this journey - although the authorities do indeed KNOW this disease, I have seen that they take these STANDS and then years down the line end up saying "oops, it's not quite the way we thought it was!" This is what happend in 2010 with the MCAS diagnosis concensus by the WHO = they had to EAT CROW and admit that they were WRONG!!! In the early 80s, Drs. Roberts and Oates wrote an impressive article on the biochemical diagnosis of mastocytosis. In that article they clearly state their theory of a Proliferative form and an Activation Form!!! it took 25 years for the present researchers to ADMIT THEY WERE WRONG!!!

It will be interesting to see what stand they take in another 25 years!!!!!

I hope this helps!

lisa

Title: Re: please help me understand tryptase testing
Post by peter on 05/23/14 at 17:30:18

Lisa lets try to cut that 25 years back a bit
Bone marrow very strong positive cd117 on mast cells is on immature mast cells
I only had (6) murture spindle shape mast cells so it didn't come from
The murture mast cells now I have NO cd117 in the bone marrow
The only possible way that could happen is

Now for tryptase in IgE venom anaphylaxis with clonal mast cells a spike of tryptase of 200 mean the number of mast cells increase as you sead tryptase show mast cell numbers in the body IF so IgE venom anaphylaxis with clonal mast cells that are cd25 would be mast cell perforation