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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.
In the citing paper
“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.
In the citing paper
“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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T Cells Expressing Chimeric Antigen Receptors Can Cause Anaphylaxis in Humans
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BackgroundDiagnosis of immediate allergic reactions to beta‐lactam antibiotics
Torres, M. J., Blanca, M., Fernández, J., Romano, A. G., Weck, A. D., Aberer, W., Brockow, K., Pichler, W. J., Demoly, P. M., for, E. N. D. A., et al. (2003) · Allergy · doi:10.1034/j.1398-9995.2003.00280.x · Cited by 527
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Self-citationThe mast cell and allergic diseases: role in pathogenesis and implications for therapy
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BackgroundDevelopment of a new, more sensitive immunoassay for human tryptase: use in systemic anaphylaxis
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Self-citationLaboratory Investigation of Deaths Due to Anaphylaxis
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Self-citationProtease-activated receptors: sentries for inflammation?
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BSACI guidelines for the management of drug allergy
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Schwartz, L. B. (1994) · Current Opinion in Immunology · doi:10.1016/0952-7915(94)90039-6 · Cited by 212
Self-citationAllergic reactions to isosulfan blue during sentinel node biopsy—a common event
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MethodThe mast cell and mast cell disease
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BackgroundTryptase genetics and anaphylaxis
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“Thus, serum b-tryptase levels (measured by an enzyme-linked immunosorbent assay) often are used to diagnose allergic patients who are undergoing systemic anaphylaxis or anaphylactoid reactions (131, 132).”
MethodMonitoring the allergic inflammation
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“Histamine (8, 24, 25) Short half-life, poor stability in serum”
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“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).”
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Tryptase and histamine release during aspirin-induced respiratory reactions
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Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep
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“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 109
A new radioimmunoassay for human mast cell tryptase using monoclonal antibodies
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Self-citationAllergic Transfusion Reactions
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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 96
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
“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
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“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 92
“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
[6] Tryptase: A mast cell serine protease
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Tryptase Levels Are Not Increased during Vancomycin-induced Anaphylactoid Reactions
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Human mast cell tryptase attenuates the vasodilator activity of calcitonin generelated peptide
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SERUM TRYPTASE AND THE LABORATORY DIAGNOSIS OF SYSTEMIC MASTOCYTOSIS
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Self-citationProtamine and Protamine Reactions
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“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.”
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“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.”
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“Therefore, the peak serum concentration of tryptase may have been missed (1, 52).”
BackgroundAnaphylactoid shock – a common cause of death in heroin addicts?
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Anaphylactic Shock after Insect-Sting Challenge in 138 Persons with a Previous Insect-Sting Reaction
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“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.”
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“Therefore, the best time point to obtain blood for MCT determination is 1—2 h after the start of the allergic reaction (17, 21).”
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“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
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“for elevation of serum tryptase levels to occur [9, 11].”
Basal serum tryptase level correlates with severity of hymenoptera sting and age.
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Biochemical Diagnosis of Systemic Mast Cell Disorders
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Mental stress‐induced hemoconcentration: Sex differences and mechanisms
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“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…”
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Preliminary report: complement activation in wasp-sting anaphylaxis
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Putative roles of inflammation in the dermatopathology of sulfur mustard
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“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
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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