Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis.
Open accessAbstract
Tryptase, a neutral protease of human mast cells, is a potentially important indicator of mast cell involvement in various clinical conditions. The current study examined the time course of appearance and disappearance of tryptase in the circulation after an anaphylactic event and the stability of both endogenous and exogenous tryptase in terms of freeze-thawing and temperature. The peak level of tryptase after an experimentally induced systemic anaphylactic reaction occurred 1-2 h after the initiating bee sting in each of three subjects, in contrast to histamine levels which peaked at 5-10 min. In some cases elevated levels of tryptase may not be detected during the initial 15-30 min. Tryptase levels then declined under apparent first order kinetics with a t1/2 of approximately 2h. Similar disappearance kinetics were observed for two subjects presenting in the emergency room with immediate type reactions, one with severe asthma after indomethacin ingestion, the other with systemic anaphylaxis after a bee sting. Histamine levels declined rapidly and were back to baseline by 15-60 min. Measured levels of tryptase in serum or plasma were not diminished by up to four freeze-thaw cycles. Incubation of serum samples taken from subjects with elevated levels of tryptase at 22 and 37 degrees C indicated that greater than 50% of endogenous tryptase was still detected after 4 d. Purified tryptase added to serum or plasma and incubated as above was less stable: approximately 50% of exogenous tryptase in serum and approximately 15% in plasma was detected after 2d of incubation. Therefore, optimally samples should be stored frozen, but even those stored at room temperature for up to 4 d should be satisfactory. The best time to obtain samples for tryptase determinations is 1-2 h after the precipitating event, but depending on the magnitude of the initial response elevated levels of tryptase may be present in the circulation for several hours.
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The most specific and reliable indicator of systemic mast cell activation is a transient, event-related, substantial rise in serum tryptase above the patient's own baseline.
“the most specific and reliable marker of systemic MC activation is an acute and substantial event-related (transient) increase in the serum tryptase level over the individual’s baseline value.”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [16]
The Introduction says tryptase selectively indicates mast-cell activation, and the Results show an event-related rise followed by a decline after venom challenge. But the paper does not establish that a substantial rise in serum tryptase over an individual’s own baseline is the most specific and reliable marker; its before-and-after challenge measurements used plasma, and its Methods describe fixed ranges for elevated levels. No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAlthough prior literature and specialized-center experience made tryptase the biomarker of choice for defining anaphylaxis and MCAS, no diagnostic threshold existed.
“although it was clear that tryptase is the biomarker of choice to define anaphylaxis and thus MCAS based on previous literature data and experience in specialized centers [12–18], a diagnostic threshold was missing.”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [16]
The Introduction and Discussion describe circulating tryptase as a useful, relatively selective indicator of mast-cell activation and report its clinical use in suspected anaphylaxis. The paper does not discuss MCAS or establish tryptase as its biomarker of choice. Its Methods give ranges for normal and elevated tryptase, so it does not support an unqualified claim that no threshold existed, although it does not set out a diagnostic threshold for MCAS. (LLM, conf=0.85)
Experimental — accuracy not yet measuredTryptase has repeatedly been described as the most specific and reliable biomarker of severe systemic mast cell activation in daily practice.
“tryptase has been repeatedly described as the most specific and reliable biomarker of severe systemic MC activation in daily practice [12–18].”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [16]
The Introduction (page not provided) says tryptase selectively indicates mast-cell activation and is more clinically practical to measure than histamine; the Discussion describes cases where testing helped confirm anaphylaxis. The paper does not establish that tryptase is the most specific and reliable biomarker in daily practice, and it notes that elevations may be missed early after a reaction. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn the work-up of anaphylaxis, BST levels raise significantly after the episode due to considerable release by MC and are expected to return to baseline at least after 24 h.
“In the work-up of anaphylaxis, BST levels raise significantly after the episode due to the considerable release by MC and is expected to turn to the baseline value at least after 24 h (28, 29).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [29]
The Results report elevated tryptase after anaphylaxis, and the Introduction identifies tryptase as a mast-cell granule protein. The Discussion says levels decline with an approximately 2-hour half-life and may remain elevated for several hours, but it does not establish that they return to an individual's baseline at 24 hours. The indexed passages provide no page numbers. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDuring and soon after a severe anaphylactic event, serum tryptase rises substantially above the individual's baseline.
“during and shortly after a severe anaphylactic event where MC release large amounts of tryptase, the serum tryptase level increases substantially over the individual’s baseline (Fig. 1) [12–17].”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [16]
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“Mast cell tryptase, a serine protease stored in the mast cell granules and released together with histamine, is relatively stable post-mortem and can be found in blood from a few minutes up to several hours after mast cell degranulation [2].”
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“Histamine (8, 24, 25) Short half-life, poor stability in serum”
BackgroundTryptase Inhibition Blocks Airway Inflammation in a Mouse Asthma Model
Oh, S., Pae, C. I., Lee, D.-K., Jones, F., Chiang, G. K. S., Kim, H.-O., Moon, S., Cao, B., Ogbu, C. O., Jeong, K.-W., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.4.1992 · Cited by 131 · see citing works
“The serine protease tryptase, localized in mast cell granules, constitutes up to 25% of the total mast cell protein (1, 2) and may play a key role in the pathogenesis of asthma and other allergic disorders (3, 4).”
BackgroundTryptase, a mediator of human mast cells
Schwartz, L. B. (1990) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(05)80222-2 · Cited by 129 · see citing works
Self-citationWeiler, C. R., Austen, K. F., Akin, C., Barkoff, M. S., Bernstein, J. A., Bonadonna, P., Butterfield, J. H., Carter, M., Fox, C. C., Maitland, A., et al. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.08.023 · Cited by 123 · see citing works
Le, Q. T., Lyons, J. J., Naranjo, A. N., Olivera, A., Lazarus, R. A., Metcalfe, D. D., Milner, J. D., & Schwartz, L. B. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190701 · Cited by 126 · see citing works
Schwartz, L. B., Min, H.-K., Ren, S., Xia, H.-Z., Hu, J., Zhao, W., Moxley, G., & Fukuoka, Y. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.11.5667 · Cited by 120 · see citing works
Self-citationHypersensitivity to Biological Agents—Updated Diagnosis, Management, and Treatment
Galvão, V. R., & Castells, M. (2015) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2014.12.006 · Cited by 118 · see citing works
Cianferoni, A., Novembre, E. M., Mugnaini, L., Lombardi, E., Bernardini, R., Pucci, N., & VIERUCCI, A. (2001) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)62318-6 · Cited by 117 · see citing works
Tryptase and histamine release during aspirin-induced respiratory reactions
Bosso, J. V., Schwartz, L. B., & Stevenson, D. D. (1991) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(91)90238-j · Cited by 114 · see citing works
Self-citationFisher, M. M., & Baldo, B. A. (2000) · Anaesthesia and Intensive Care · doi:10.1177/0310057x0002800207 · Cited by 114 · see citing works
Expression of α-tryptase and β-tryptase by human basophils
Jogie-Brahim, S., Min, H.-K., Fukuoka, Y., Xia, H.-Z., & Schwartz, L. B. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.02.032 · Cited by 113 · see citing works
Self-citationClinical utility of tryptase levels in systemic mastocytosis and associated hematologic disorders
Schwartz, L. B. (2001) · Leukemia Research · doi:10.1016/s0145-2126(01)00020-0 · Cited by 110 · see citing works
Self-citationElevated Postmortem Tryptase in the Absence of Anaphylaxis
Randall, B. B., Butts, J. D., & Halsey, J. F. (1995) · Journal of Forensic Sciences · doi:10.1520/jfs15343j · Cited by 110 · see citing works
Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep
Elrod, K., MOORE, W. R., Abraham, W. M., & Tanaka, R. D. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.2.9607012 · Cited by 109 · see citing works
“The presence of tryptase in biological matrices is an indicator of mast cell degranulation in anaphylaxis and allergic reaction ( 17 , 18).”
BackgroundHuang, R., Blom, T., & Hellman, L. (1991) · European Journal of Immunology · doi:10.1002/eji.1830210706 · Cited by 108 · see citing works
A new radioimmunoassay for human mast cell tryptase using monoclonal antibodies
Enander, I., Matsson, P., Nystrand, J., Andersson, A., Eklund, E., Bradford, T. R., & Schwartz, L. B. (1991) · Journal of Immunological Methods · doi:10.1016/0022-1759(91)90062-k · Cited by 100 · see citing works
Self-citationAllergic transfusion reactions: an evaluation of 273 consecutive reactions.
Domen, R. E., & Hoeltge, G. A. (2003) · PubMed · doi:10.5858/2003-127-0316-atr · Cited by 98 · see citing works
Coyne, D. W., Adkinson, F., Nissenson, A. R., Fishbane, S. N., Agarwal, R., Eschbach, J. W., Michael, B., Folkert, V. W., BATLLE, D. C., Trout, J. R., et al. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00703.x · Cited by 98 · see citing works
The Level of Tryptase in Human Tears
Butrus, S. I., Ochsner, K. I., Abelson, M. B., & Schwartz, L. B. (1990) · Ophthalmology · doi:10.1016/s0161-6420(90)32362-x · Cited by 97 · see citing works
Self-citationPaired acute‐baseline serum tryptase levels in perioperative anaphylaxis: An observational study
Vitte, J., Amadei, L., Gouitaa, M., Mezouar, S., Zieleskiewicz, L., Albanese, J., Bruder, N., Lagier, D., Mertès, P. M., Mège, J., et al. (2019) · Allergy · doi:10.1111/all.13752 · Cited by 94 · see citing works
“Mature tryptase was measured in the VCU Laboratory using the biotin‐conjugated G5 monoclonal anti‐tryptase IgG for detection and the B12 monoclonal anti‐tryptase IgG for capture.(9,12,25) Consecutive acute samples from 42 patients were retrospectively selected from the study population.”
BackgroundMethodSelf-citationAn ongoing Confidential Enquiry into asthma deaths in the Eastern Region of the UK, 2001–2003
HARRISON, B., STEPHENSON, P., Mohan, G., & Nasser, S. M. (2005) · Primary Care Respiratory Journal · doi:10.1016/j.pcrj.2005.08.004 · Cited by 91 · see citing works
“tryptase obtained up to 72 hours post-mortem could be used to identify this group of patients [32,33].”
MethodMast cell tryptase in postmortem serum—reference values and confounders
Edston, E., Eriksson, O., & van Hage, M. (2006) · International Journal of Legal Medicine · doi:10.1007/s00414-006-0101-2 · Cited by 91 · see citing works
“However, previous experience has shown that elevated tryptase values in femoral blood are rare in sudden cardiovascular fatalities [6], and in rapid deaths occurring within minutes of the assault even if mast cells were degranulated, at least in theory, tryptase would not have had time to be released into the circulat…”
BackgroundFatal Anaphylaxis Due to Fire Ant Stings
Prahlow, J. A., & Barnard, J. J. (1998) · American Journal of Forensic Medicine & Pathology · doi:10.1097/00000433-199806000-00007 · Cited by 89 · see citing works
[6] Tryptase: A mast cell serine protease
Schwartz, L. B. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)44008-5 · Cited by 89 · see citing works
Self-citationSwystun, V. A., Gordon, J., Davis, E. B., Zhang, X., & Cockcroft, D. W. (2000) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2000.107396 · Cited by 88 · see citing works
Tryptase Levels Are Not Increased during Vancomycin-induced Anaphylactoid Reactions
Renz, C. L., Laroche, D., Thurn, J. D., Finn, H. A., Lynch, J. P., Thisted, R. A., & Moss, J. (1998) · Anesthesiology · doi:10.1097/00000542-199809000-00010 · Cited by 87 · see citing works
Human mast cell tryptase attenuates the vasodilator activity of calcitonin generelated peptide
Walls, A. F., Brain, S. D., Desai, A., Jose, P. J., Hawkings, E., Church, M. K., & Williams, T. J. (1992) · Biochemical Pharmacology · doi:10.1016/0006-2952(92)90498-8 · Cited by 87 · see citing works
SERUM TRYPTASE AND THE LABORATORY DIAGNOSIS OF SYSTEMIC MASTOCYTOSIS
Schwartz, L. B., & Irani, A.-M. A. (2000) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70300-2 · Cited by 86 · see citing works
Self-citationProtamine and Protamine Reactions
Park, K. W. (2004) · International Anesthesiology Clinics · doi:10.1097/00004311-200404230-00011 · Cited by 85 · see citing works
“Serum tryptase is an indicator of mast cell involvement in an anaphylactoid reaction.(29) It is released during an anaphylactoid reaction and may be detected for more than 1 hour after the reaction.”
BackgroundMayer, D. E., Krauskopf, A., Hemmer, W., Moritz, K., Jarisch, R., & Reiter, C. G. (2011) · Forensic Science International · doi:10.1016/j.forsciint.2011.05.020 · Cited by 84 · see citing works
“Although there seems to be a correlation between histamine and tryptase in the living [14], we found only a modest non-significant correlation between those two parameters in post mortem samples.”
BackgroundInfluentialHeier, T., & Guttormsen, A. B. (2000) · Acta Anaesthesiologica Scandinavica · doi:10.1034/j.1399-6576.2000.440702.x · Cited by 82 · see citing works
“Therefore, the peak serum concentration of tryptase may have been missed (1, 52).”
BackgroundAnaphylactoid shock – a common cause of death in heroin addicts?
Edston, E., van Hage, M., & Edston, E. (1997) · Allergy · doi:10.1111/j.1398-9995.1997.tb01256.x · Cited by 81 · see citing works
Thomas, V. A., Wheeless, C. J., Stack, M. S., & Johnson, D. A. (1998) · Biochemistry · doi:10.1021/bi972119z · Cited by 80 · see citing works
Ghildyal, N., Friend, D. S., Stevens, R. L., Austen, K. F., Huang, C. B., Penrose, J. F., Šali, A., & Gurish, M. F. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.3.1061 · Cited by 80 · see citing works
Vitte, J., Sabato, V., Tacquard, C., Garvey, L. H., Michel, M., Mertes, P.-M., Ebo, D. G., Schwartz, L. B., & Castells, M. C. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.03.011 · Cited by 79 · see citing works
Self-citationRenz, H. E., Biedermann, T., Bufe, A., Eberlein, B., Jappe, U., Ollert, M. W., Petersen, A., Kleine‐Tebbe, J., Raulf, M., Saloga, J., et al. (2010) · Allergo Journal · doi:10.1007/bf03362255 · Cited by 79 · see citing works
Anaphylactic Shock after Insect-Sting Challenge in 138 Persons with a Previous Insect-Sting Reaction
van der Linden, P.-W. G., Struyvenberg, A., Kraaijenhagen, R. J., Hack, C. E., & van der Zwan, J. K. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-118-3-199302010-00001 · Cited by 79 · see citing works
Anaphylactic deaths in Auckland, New Zealand: a review of coronial autopsies from 1985 to 2005
Low, I., & Stables, S. R. (2006) · Pathology · doi:10.1080/00313020600820831 · Cited by 78 · see citing works
“The peak level of serum tryptase occurs around 2 hours from onset of anaphylaxis, and then declines following first-order kinetics with a half-life of around 2 hours.(12) Therefore, blood samples should ideally be collected within hours of symptom onset.”
BackgroundDybendal, T., Guttormsen, A. B., Elsayed, S., Askeland, B., Harboe, T., & Florvaag, E. (2003) · Acta Anaesthesiologica Scandinavica · doi:10.1046/j.1399-6576.2003.00237.x · Cited by 78 · see citing works
“Therefore, the best time point to obtain blood for MCT determination is 1—2 h after the start of the allergic reaction (17, 21).”
BackgroundGraft, D. F. (2006) · Medical Clinics of North America · doi:10.1016/j.mcna.2005.08.006 · Cited by 76 · see citing works
“An elevated serum tryptase, which signals mast cell degranulation, provides additional evidence for anaphylaxis [46].”
BackgroundUsefulness of serum mast cell–specific chymase levels for postmortem diagnosis of anaphylaxis
Nishio, H., Takai, S., Miyazaki, M., Horiuchi, H., Osawa, M., Uemura, K., Yoshida, K., Mukaida, M., Ueno, Y., & Suzuki, K. (2005) · International Journal of Legal Medicine · doi:10.1007/s00414-005-0524-1 · Cited by 76 · see citing works
“for elevation of serum tryptase levels to occur [9, 11].”
Basal serum tryptase level correlates with severity of hymenoptera sting and age.
Kucharewicz, I., Bodzenta‐Łukaszyk, A., Szymanski, W., Mroczko, B., & Szmitkowski, M. (2007) · PubMed · Cited by 75 · see citing works
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Borer‐Reinhold, M., Haeberli, G., Bitzenhofer, M., Jandus, P., Hausmann, O., Fricker, M., Helbling, A., & Müller, U. (2011) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2011.03848.x · Cited by 73 · see citing works
Biochemical Diagnosis of Systemic Mast Cell Disorders
Roberts, L. J., & Oates, J. A. (1991) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12468945 · Cited by 74 · see citing works
Mast cell tryptase in dermal neurogenic inflammation
Schmelz, M., ZECK, Raithel, & RUKWIED (1999) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1999.00514.x · Cited by 73 · see citing works
Mental stress‐induced hemoconcentration: Sex differences and mechanisms
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Utilization of Serum Tryptase and Immunoglobulin E Assay in the Postmortem Diagnosis of Anaphylaxis
Horn, K. D., Halsey, J. F., & Zumwalt, R. E. (2004) · American Journal of Forensic Medicine & Pathology · doi:10.1097/01.paf.0000113814.56572.de · Cited by 71 · see citing works
“Serum mast cell tryptase is a reliable indicator of systemic mast cell activation (such as occurs in anaphylaxis) in the living patient and has been used in the postmortem diagnosis of anaphylaxis in recent years.(3,4) A recent study found that evidence of mast cell activation (as determined by elevation of serum tryp…”
BackgroundInfluentialBonamichi-Santos, R., & Castells, M. (2016) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-016-8556-5 · Cited by 70 · see citing works
Preliminary report: complement activation in wasp-sting anaphylaxis
van der Linden, P. W. G., Kerckhaert, J. A. M., van der Zwan, J. C., Hack, C. E., & Struyvenberg, A. (1990) · The Lancet · doi:10.1016/0140-6736(90)92272-j · Cited by 70 · see citing works
Putative roles of inflammation in the dermatopathology of sulfur mustard
Cowan, F. M., & Broomfield, C. A. (1993) · Cell Biology and Toxicology · doi:10.1007/bf00755599 · Cited by 70 · see citing works
“The protease tryptase is one of the chief components of mast cell granules (Schwartz et al., 1989) and is also part of a protease cascade that can activate procollagenase (Krejci et al., 1992).”
Background
- Authors
- Schwartz, L. B., Yunginger, J. W., Miller, J., Bokhari, R., & Dull, D.
- Affiliations
- Virginia Commonwealth University Medical Center (US)
- Mayo Clinic (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1989-05-01
- Volume
- 83
- Issue
- 5
- Pages
- 1551-1555
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC303860
- OpenAlex
- W2024275029
- Cited by
- 456
- References
- 18
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 14 · 2020: 6 · 2019: 16 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 12 · 2014: 20 · 2013: 9 · 2012: 4
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI20487, AI-72621)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- tryptase, mast cells, anaphylaxis, bee stings, histamine, freeze-thaw cycles, sample storage, immediate hypersensitivity, serum biomarkers
- MeSH terms
- Adult, Anaphylaxis, Body Temperature, Child, Preschool, Female, Freezing, Histamine Release, Humans, Kinetics, Mast Cells, Peptide Hydrolases, Temperature
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