Patient questions: Everything you wanted to know about tryptase

I get a lot of questions about tryptase.

Tryptase is one of the most well characterized mast cell mediators and the first to be unique to mast cells. Serum tryptase is the most well known test for systemic mastocytosis and anaphylaxis. But mast cell patients sometimes test negative, complicating their lives and care.

There are a lot of reasons why mast cell patients test negative for tryptase. One reason is that a lot of the understanding of anaphylaxis hinged upon the ability of mediators to get quickly to the bloodstream to quickly spread to various organ systems. While this does happen, not all mediators move at the same speed. Tryptase is released from granules as large complexes with other mediators, like heparin. It takes time for it to dissociate enough to be active.

Tryptase also does a lot of things and breaks down lots of things. If there are things for it to break down in the immediate environment, it will still break them down whether or not you are having anaphylaxis. Eventually, the tryptase that wasn’t used up breaking things down gets to the bloodstream. This is why the ideal time to test for tryptase in blood is about 90-120 minutes after an allergic event/severe reaction/anaphylaxis. Following severe reaction/anaphylaxis, it can take about two weeks for tryptase to return to baseline.

The reason that most patients with systemic mastocytosis have high tryptase levels is because they have more mast cells and many mast cells secrete tryptase at rest. This means that even if they aren’t activated, they will still release tryptase regularly. The reason why baseline tryptase level is such an important marker for SM is because it distinguishes mastocytosis from anaphylaxis.

However, we have learned a lot about tryptase in the last several years, and it doesn’t seem like all mast cells secrete tryptase all the time. Mast cells are heavily influenced by their environment and the cells around them. Some mast cells make more tryptase than others and some release tryptase regularly and some don’t.

About 80-90% of SM patients have a baseline tryptase over 20 ng/ml. This means they tested over 20 ng/ml on two separate occasions when they had not recently had a severe event. But not all SM patients have elevated tryptase, but that doesn’t mean they don’t have more mast cells than usual. It is possible that their mast cells are concentrated in places in the body where tryptase will be used up before it gets to the bloodstream or that it will take too long to get there for the test to catch it. There is some evidence that tryptase testing is less reliable in overweight and obese women, and I’m sure that’s true. Some mast cells live in adipose tissue and that tissue is harder for large molecules to move through, like tryptase.

Our understanding of MCAS is that there is aberrant mast cell behavior without an abnormal number of mast cells. These patients generally have repeat negative biopsies and so the assumption is that they definitely don’t have SM. But tryptase is a crummy test and I think as a community we can’t really know if they have too many mast cells until we have more robust tests. I’m not saying MCAS patients have too many mast cells, but I’m saying I don’t really trust tryptase for detection of reaction/anaphylaxis in MCAS patients or, to be frank, in anyone.

So why do we still use tryptase if it’s a crummy test? It’s not a crummy test for everything. In particular, it is a very good indicator of disease progression (ISM to SSM to ASM) in patients who have a lot of mast cells. A steadily increasing tryptase level means that there is increased proliferation and can indicate moving to a state where organ damage is more likely. So it is helpful for those people. It’s not helpful for everyone else.

Tryptase testing is not affected in a meaningful way by any medications that I can think of. Mast cell stabilizers can decrease degranulation, but tryptase can also be released in other ways, and there has not been any demonstration that mast cell stabilizers are effective enough to affect this test. Antihistamines/other meds/steroids don’t affect tryptase level.

There was a consensus paper that came out several years ago in which it was posited that an increase in tryptase level of 2 ng/ml + 2% from baseline was indicative of mast cell activation and could be used in the diagnosis of MCAS. This is not widely agreed to in the US and the data supporting this has never been published so I personally understand the reluctance of providers to acknowledge this as a marker of mast cell activation.

The other big reason why mast cell patients may test normal for tryptase is that their reactions/anaphylaxis are not mediated by a pathway that triggers tryptase release like IgE does.  IgG activation and other pathways do not always demonstrate tryptase release.

I think I got everything. If you have more questions about tryptase, let me know.

14 Responses

  1. Kim May 27, 2016 / 9:05 pm

    Thanks Lisa, this is the most comprehensive explanation about Tryptase that I’ve ever read. Please keep us updated.
    All the best,
    Kim

  2. Tim Miller May 27, 2016 / 11:16 pm

    So I have an initial tryptase test from 3 years ago at 21. A the time, I had a negative double BM biopsy done at Mayo for SM. Each year, my tryptase has increase by 1-2. It is now currently been tested at 24. What is the significance of this? Afrin just says to keep an eye on it as the slight increase is incidental. At what point does the gradual increase become concerning?

    Thanks!

  3. Nancie May 27, 2016 / 11:42 pm

    Thanks once again for an explanation of tryptase that our family can understand. The article will help my sister to understand why the Drs haven’t been able to diagnosis MCAS due to her low tryptase levels. Additionally, your explanation that “A steadily increasing tryptase level means that there is increased proliferation and can indicate moving to a state where organ damage is more likely,” was helpful to me since my tryptase has recently climbed to 677. This was a surprise to me since I just finished 2 months of Midostaurin. The first month my tryptase dropped to 322 and after the second month, it climbed to an all time high of 677. At this point, I am unsure if proceeding with more Mido is advisable (as requested by my oncologist). Your thoughts on this are appreciated.

  4. Bailey May 28, 2016 / 2:34 am

    So basically a person can have MCAS or MMAS and never show an elevated tryptase?

    • Lisa Klimas May 28, 2016 / 11:55 pm

      Yes. Or SM. Or any mast cell disease.

  5. Sandra Corbaz May 28, 2016 / 6:08 am

    Hi Lisa, and thanks for this very comprehensive article on tryptase. What is the effect on the system (body) of elevated tryptase (like low serotonin can cause depression, or histamine flooding causes ana)? What does tryptase do?
    Many thanks, Sandra

  6. Kathy May 28, 2016 / 7:51 am

    Lisa,
    Thanks for such a great explanation of tryptase. You have explained it more thoroughly than any doc has been able to. You have a gift for this!
    Kathy

  7. Natalie May 28, 2016 / 1:33 pm

    This post is so dead on and very thorough.
    I happened to stumple upon an article on mayo. It was one of the first times I’ve seen on mayo especially recognotion that tryptase is not relaible.
    Maybe I’m stating something that everyone on this community already knows but it looks like they’ve developed a test to properly test and diagnose Leukotrienes. Maybe Im not sayong this all properly but check this article put about new testing for SM..

    • Lisa Klimas May 28, 2016 / 11:54 pm

      Hi, Natalie. Thanks for commenting. You are correct that there is a test now for urinary leukotrienes that is useful for diagnosis of mast cell activation. There was also a recent publication on this method, which is especially helpful. I will be discussing this in an upcoming post on urinary mediator testing. Thanks!

  8. Yvonne Branchflower May 28, 2016 / 3:03 pm

    Lisa, thank you for this post. I was under the mistaken notion that cromolyn reduced tryptase.

  9. Melanie Pickard May 28, 2016 / 4:36 pm

    I have had Systemic Mastocytosis for 33 years. I had my very first Tryptase level done just 2 yrs. ago. It was in the 900’s. It continued to climb and got up to 1295. I was put on midostaurin and was only on it 15 days in Feb.2016. Had to stop med due to high Alkaline phosphatase level. But in 15 days it did bring the tryptase down into the 900’s. I just started blu-285 60mg. daily. Have taken 12 doses of the blu and tryptase has dropped down into the 500’s.

  10. Christal Janis May 29, 2016 / 6:34 pm

    This is a great article but way over my head. What does the SM initials mean, it was first mentioned in the 6th paragraph? Am I to understand that there is no help available for a person with high Tryptase levels? There is a old nasal spray called Nasal Crom 5.2 mg of Cromolyn sodium. It was a RX for many years but is over the counter. Has this very effective, with none of the usual side affects in the current ones available now, been used to treat MCD? Thank you for any help/

    • Lisa Klimas May 29, 2016 / 7:19 pm

      SM is systemic mastocytosis. There are many treatment options for mast cell patients, I have written hundreds of posts on these diseases and treatment for them. Tryptase is a marker of mast cell count and activity. There is treatment for these diseases but only chemo drugs decrease mast cell count and therefore tryptase. Tryptase level itself does not require treatment, it is the associated disease that requires treatment.

      Cromolyn is a mainstay of mast cell treatment.

  11. Nancie May 29, 2016 / 9:11 pm

    Melanie Pickard – I am very interested in your Mido and blu-285 60 mg experience. As posted earlier, my tryptase initially dropped with Mido and then elevated again to 677. My Dr. wants me to continue and I am hesitant (at an impasse right now & need to make a decision). What I really need to find is a Dr, anywhere within the states, that can provide diagnosis & advise on maintenance of ASM. Are you willing to pass on your Drs name?

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