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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 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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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“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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Citations
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“Studies on timing of release of the mast cell mediators, histamine and tryptase, show much earlier systemic accumulation of histamine with a half-life of 2 min, whereas tryptase levels in the blood are maximal at 1–2 h and then decline thereafter, with a half-life of 2 h (6, 7).”
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“specific b-tryptase assays are not as readily available.(35,36) However, caution is advised when relying on tryptase levels to exclude or confirm a diagnosis of anaphylaxis.”
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“For evaluation of mast-cell activation by measuring serum concentration of the mediator, tryptase appears to be more appropriate than other mediators, such as histamine, prostaglandin D2, and leukotrienes C4 and D4, because of its stability in systemic circulation and specificity to mast cells (12).”
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Pedrosa, M., Prieto, A., Sala-Cunill, A., on Behalf of the Spanish Group for the Study of Bradykinin-Mediated Angioedema (SGBA) and the Spanish Committee of Cutaneous Allergy (CCA), Members of the Spanish Group for the Study of Bradykinin-Mediated Angioedema (SGBA):, Caballero, T., Baeza, M. L., Cabañas, R., Campos, A., Cimbollek, S., et al. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.949300 · Cited by 27
Management and Prevention of Anaphylaxis
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“During bee-sting induced anaphylaxis, tryptase levels in the blood stream are maximal at 60±120 min, whereas those of histamine are maximal at 5 min.(25) Tryptase levels then decline with a half-life of 1.”
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“In addition. tryptase has a longer half-life than histamine in plasma [ 32 ].”
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Brown, S. G. A., & Stone, S. F. (2011) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2011.03893.x · Cited by 22
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“…observed during the activation and degranulation of mast cells. β -tryptase is selectively concentrated in the secretory granules of mast cells and is released only after degranulation, thus the presence of a high concentration in the bloodstream is a clear expression of mast cell activation (2).”
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“While it is known that tryptase is released by human mast cells together with histamine in vitro [13], there are discrepancies between the detection of these mediators in clinical disease [18,19] attributed to the fact that mature tryptase occurs in complex with proteoglycan, which Figure 1.”
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Fatal Adverse Reaction to Ketorolac Tromethamine in Asthmatic Patient
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“after the onset of anaphylaxis or in people experiencing rapidly fatal anaphylaxis.(27,31) However, elevations in the”
BackgroundSerum tryptase levels in sudden infant death syndrome in forensic autopsy cases
Nishio, H., & Suzuki, K. (2003) · Forensic Science International · doi:10.1016/j.forsciint.2003.09.011 · Cited by 22
Characterization of a Tryptase mRNA Expressed in the Human Basophil Cell Line KU812
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“It is recommended that serum tryptase be checked as soon as possible (15 minutes to 3 hours) after the onset of anaphylaxis because it peaks near the onset of anaphylaxis and has a half-life of 2 hours.(42) A tryptase level greater than 12 mcg/L is indicative of anaphylaxis, thus the observed level of 5.”
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Edston, E., van Hage-Hamsten, M., & Johansson, S. G. O. (1996) · Allergy · doi:10.1111/j.1398-9995.1996.tb00160.x · Cited by 19
Postmortem Diagnosis of Anaphylaxis
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Release of soluble tryptase but only minor amounts of chymase activity from cutaneous mast cells
Kivinen, P. K., Kaminska, R., Naukkarinen, A., Harvima, R. J., Horsmanheimo, M., & Harvima, I. T. (2001) · Experimental Dermatology · doi:10.1034/j.1600-0625.2001.100404.x · Cited by 19
“The release of tryptase together with histamine upon an allergic reaction to skin chamber fluid and serum has been shown in several studies where the release kinetics of tryptase is slower than that of histamine (32, 33).”
ResultPeanut allergen inhibition prevents anaphylaxis in a humanized mouse model
Alakhras, N. S., Shin, J.-H., Smith, S. A., Sinn, A. L., Zhang, W., Hwang, G., Sjoerdsma, J. N., Bromley, E. K., Pollok, K. E., Bilgiçer, B., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.add6373 · Cited by 19
“Released tryptase can be detected in human serum within minutes after the first symptoms of anaphylaxis and can be detected for 24 to 48 hours (34, 46, 47).”
BackgroundCapecitabine-induced ventricular fibrillation arrest: Possible Kounis syndrome
Kido, K., Adams, V. R., Morehead, R. S., & Flannery, A. H. (2015) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155214563814 · Cited by 18
“Thus the level was delayed and may have been within normal range due to its short half-life of about 90min.(17) It has been suggested that the best time to obtain tryptase levels is 1–2 h after the event.”
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Sanz, M. L., Gamboa, P. M., Figueroa, B. E. G., & Ferrer, M. (2010) · Chemical immunology/Fortschritte der Allergielehre/Progress in allergy/Chemical immunology and allergy · doi:10.1159/000315947 · Cited by 18
Anaphylaxis in the emergency department: a paediatric perspective
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Structure and Function of Human Mast Cell Tryptase
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“Of note, α-protryptase is released constitutively from MCs into plasma [18], while specific release of β-tryptase during anaphylaxis has been reported [19].”
BackgroundParsons, I., Stacey, M. J., Faconti, L., Hill, N. E., O'Hara, J. P., Walter, E. J., Farukh, B., McNally, R., Sharp, H., Patten, A., et al. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04645-0 · Cited by 16
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“In cases of collapse assumed to be due to anaphylaxis, the increased MC tryptase levels 1–4 h after the event can be useful in confirming the diagnosis [66,67], as well as serum allergen-specific IgE tests, and the diagnosis will be retrospectively confirmed [68,69].”
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A Novel Model of IgE-Mediated Passive Pulmonary Anaphylaxis in Rats
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“This is consistent with the time course of the same mediators following anaphylaxis in humans, and further validates the findings described in this model [13].”
Death following ceftazidime-induced Kounis syndrome
Kitulwatte, I. D. G., Gangahawatte, S. D. S., Perera, U., & Edirisinghe, P. (2017) · Medico-Legal Journal · doi:10.1177/0025817217695904 · Cited by 16
“A postmortem study conducted on cases of fatal anaphylaxis in the United Kingdom showed that 23 of 56 deaths had no macroscopic postmortem findings.(5) Positive autopsy findings in fatal anaphylaxis include cutaneous erythema, upper airway oedema, mucous plugging of the bronchi, hyperinflation of the lungs, petechial…”
BackgroundInfluentialBlank, S., Pehlivanli, S., Methe, H., Schmidt‐Weber, C. B., Biedermann, T., Horny, H., Kristensen, T. K., Amar, Y., Köberle, M., Brockow, K., et al. (2019) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2019.06.021 · Cited by 16
Clinical advances in mastocytosis
Genovese, A., Spadaro, G., Triggiani, M., & Marone, G. (1995) · International Journal of Clinical & Laboratory Research · doi:10.1007/bf02592695 · Cited by 16
A case of anaphylactic shock possibly caused by intravesical Hexvix®
Colapaoli, L., Thorsen, J., Nopp, A., & Guttormsen, A. B. (2006) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.2006.01110.x · Cited by 16
“Serum tryptase (8, 9), a marker of mast cell activation, increased from 6.”
BackgroundComment rapporter à l’anaphylaxie l’accident observé ? Tests diagnostiques in vitro
Laroche, D., Guilloux, L., & Guéant, J. (2002) · Annales Françaises d Anesthésie et de Réanimation · doi:10.1016/s0750-7658(01)00565-2 · Cited by 16
Tryptase concentrations in bronchoalveolar lavage from patients with chronic eosinophilic pneumonia
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Cellular Inflammation in Asthma: Neutral Proteases of Mast Cells
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Risk of anaphylaxis in opioid dependent persons: effects of heroin versus substitution substance
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“It is more stable, has a longer half-life than histamine and can be detected from a few minutes up to several hours after mast cell degranulation [20,38].”
BackgroundInfluentialPerskvist, N., Söderberg, C., van Hage, M., & Edston, E. (2007) · PubMed Central · Cited by 14
Immunological Basis of Food Allergy (IgE-Mediated, Non-IgE-Mediated, and Tolerance)
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Serum tryptase: an indicator of anaphylaxis following fluorescein angiography
Butrus, S. I., Negvesky, G. J., Rivera-Velazques, P. M., & Schwartz, L. B. (1999) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s004170050256 · Cited by 14
“The half-life for the disappearance of tryptase from the circulation (1.5‐2 h) [ 5 ] is long relative to that of histamine (1‐3 min).”
BackgroundInfluentialSelf-citationDrug‐induced anaphylaxis in the emergency room
Takazawa, T., Oshima, K., & Saito, S. (2017) · Acute Medicine & Surgery · doi:10.1002/ams2.282 · Cited by 14
Part II: Chronic Urticaria/Angioedema
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Valent, P., Akin, C., & Arock, M. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-024-01124-2 · Cited by 13
Tryptase as an inflammatory marker in allergic disease and asthma
Bachelet, I., Munitz, A., & Levi‐Schaffer, F. (2005) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.1.1.63 · Cited by 13
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“Tryptase, like other inflammatory mediators, is short lived and has a half-life of about 90 min (Schwartz et al., 1989).”
BackgroundVarney, V., Nicholas, A., Warner, A., & Sumar, N. (2019) · Journal of Asthma and Allergy · doi:10.2147/jaa.s213016 · Cited by 13
Kotani, N., Kushikata, T., Matsukawa, T., Sessler, D. I., Muraoka, M., Hashimoto, H., Ishihara, H., & MATSUKI, A. (1997) · Anesthesiology · doi:10.1097/00000542-199709000-00016 · Cited by 13
The Analysis of Tryptase in Serum of Sarcoidosis Patients
Bargagli, E., Mazzi, A., Mezzasalma, F., Perrone, A. F., Olivieri, C., Prasse, A., Bianchi, N., Pieroni, M., & Rottoli, P. (2009) · Inflammation · doi:10.1007/s10753-009-9137-z · Cited by 13
“Elevated concentrations of tryptase have been found in different pathological conditions: in serum of patients with acute anaphylaxis and mastocytosis [17], in nasal lavage fluid of allergic patients, in induced sputum and BAL of patients with asthma [18] and in 2005 we found increased tryptase levels in BAL of patien…”
BackgroundIde, H., Itoh, H., & Nawa, Y. (1994) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/0167-4838(94)90198-8 · Cited by 13
Development of markers for human basophils and mast cells
Schwartz, L. B., & Kepleyb, C. (1994) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(94)90337-9 · Cited by 13
Self-citationBiology of Mast Cells and their Mediators
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An approach to iatrogenic deaths
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Mast cell tryptase in a case of anaphylaxis due to repeat antibiotic exposure
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“However, study of this enzyme has been shown to be stable for 2–4 days after acquisition [19].”
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Polycythemia vera and water–induced pruritus: evidence against mast cell involvement
Buchanan, J. G., Ameratunga, R., & Hawkins, R. C. (1994) · Pathology · doi:10.1080/00313029400169091 · Cited by 12
How to interpret mast cell tests
Waterfield, T., Dyer, E., Wilson, K. M., & Boyle, R. J. (2016) · Archives of Disease in Childhood Education & Practice · doi:10.1136/archdischild-2015-309887 · Cited by 11
“The peak level in the blood is usually measurable at 1-6 hours after the onset of anaphylaxis with tryptase having a half-life of around 2 hours and the levels returning to normal at around 24 hours (3).”
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Plasma histamine and tryptase during anaphylactoid reactions
Laroche, D., Vergnaud, M.-C., Dubois, F., & Bricard, H. (1992) · Inflammation Research · doi:10.1007/bf01997333 · Cited by 10
Drug Insight: safety of intravenous iron supplementation with sodium ferric gluconate complex
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“Of the three patients who were intolerant of SFGC, two showed a 100% increase in serum tryptase levels from baseline after SFGC infusion, indicating an allergic reaction”
BackgroundHyperthermia after cardiac surgery
Abe, K., Miyamoto, Y., & 健二, 大. (1997) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/bf03015452 · Cited by 10
Sampson, H. A. (2013) · Wiley eBooks · doi:10.1002/9781118744185.ch14 · Cited by 10
Serum Tryptase in Allergic Rhinitis: Effect of Cetirizine Treatment
Bruno, G., Andreozzi, P., Magrini, L., Santangelo, G., Graf, U., & Angelino, A. (2001) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200101400305 · Cited by 11
Haraguchi, T., Horiuchi, T., Takazawa, T., Nagumo, K., Orihara, M., & Saito, S. (2024) · Allergology International · doi:10.1016/j.alit.2024.04.005 · Cited by 9
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“Copyright © 2020 Wolters Kluwer and the statistics associated with this condition have been shown to reflect the high levels of stress among regular workers; 31% of victims held professional or administrative positions; 27% held clerical, service, or sales positions; and 38%were laborers.(10) Over the last decade, Jap…”
BackgroundTambuzzi, S., Gentile, G., Boracchi, M., Candia, D. D., Bianchi, R., & Zoja, R. (2021) · Forensic Science Medicine and Pathology · doi:10.1007/s12024-021-00373-1 · Cited by 9
“The post-mortem diagnosis of anaphylaxis differs profoundly from that in a clinical setting, which is typically supported by an increase in serum proteases within two hours of the acute event [21].”
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ANAPHYLAXIS AND FOOD HYPERSENSITIVITY
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What the clinician should know when ordering a mast cell tryptase test
Michel, M., Giusti, D., Klingebiel, C., Pham, B., & Vitte, J. (2025) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2025.03.003 · Cited by 9
Immediate hypersensitivity reactions to antineoplastic agents – A practical guide for the oncologist
Seghers, S., Teuwen, L.-A. M. N., Beyens, M. M. J., Blick, D. D., Sabato, V., Ebo, D. G., & Prenen, H. (2023) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2023.102559 · Cited by 8
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Drug-induced anaphylaxis in children.
Cardinale, F., Amato, D., Mastrototaro, M. F., Caffarelli, C., Crisafulli, G., Franceschini, F., Liotti, L., Caimmi, S. M. E., Bottau, P., Saretta, F., et al. (2019) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v90i3-s.8172 · Cited by 8
Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway
Yang, R., Wang, G., Li, L., He, H., Zheng, M., Lu, L., & Wu, S. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02621-4 · Cited by 8
ABE, T. K., Shimada, E., Takanashi, M., Takamura, T., Motoji, K., Okazaki, H., Satake, M., & Tadokoro, K. (2014) · Transfusion · doi:10.1111/trf.12586 · Cited by 8
“These phenomena are closely related to the development of anaphylaxis and increased concentrations of serum or plasma tryptase are considered as a marker of anaphylaxis.(4,5) The serum or plasma tryptase concentration in patients who developed anaphylactic transfusion reactions was observed to”
Background
Metadata
- 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 (medical) › 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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