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Cited by 371Mast cells and histamineFood Allergy and Anaphylaxis ResearchPlatelet Disorders and Treatments

The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis.

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Schwartz, L B, Sakai, K, Bradford, T R, Ren, S, Zweiman, B, Worobec, A S, Metcalfe, D D·1995·Journal of Clinical Investigation
DOI 10.1172/jci118337PMC PMC185977
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Abstract

Tryptase, a protease produced by all mast cells, was evaluated as a clinical marker of systemic mastocytosis. Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture. The B12 capture assay measured both recombinant alpha- and beta-tryptase, whereas the G5 capture assay measured primarily recombinant beta-tryptase. G5 binds with low affinity to both recombinant alpha-tryptase and tryptase in blood from normal and nonacute mastocytosis subjects, and binds with high affinity to recombinant beta-tryptase, tryptase in serum during anaphylaxis, and tryptase stored in mast cell secretory granules. B12 recognizes all of these forms of tryptase with high affinity. As reported previously, during systemic anaphylaxis in patients without known mastocytosis, the ratio of B12- to G5-measured tryptase was always < 5 and approached unity (Schwartz L.B., T.R. Bradford, C. Rouse, A.-M. Irani, G. Rasp, J.K. Van der Zwan and P.-W.G. Van der Linden, J. Clin. Immunol. 14:190-204). In this report, most mastocytosis patients with systemic disease have B12-measured tryptase levels that are elevated (> 20 ng/ml) and are at least 10-fold greater than the corresponding G5-measured tryptase level. Most of those subjects with B12-measured tryptase levels of < 20 ng/ml had only cutaneous manifestations. The B12 assay for alpha-tryptase and beta-tryptase, particularly when performed in conjunction with the G5 assay for beta-tryptase, provides a more precise measure of mast cell involvement than currently available assessments, a promising potential screening test for systemic mastocytosis and may provide an improved means to follow disease progression and response to therapy.

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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 [12]

    The Introduction reports that serum or plasma tryptase rises during insect-sting anaphylaxis and correlates with reaction severity; the Results also note preliminary evidence of increases during mast-cell-mediator attacks. But the paper does not establish that a transient rise over an individual’s own baseline is the most specific and reliable marker of systemic mast-cell activation. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Although 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 [12]

    The Introduction (page unavailable) describes tryptase measurements during insect-sting anaphylaxis that correlate with reaction severity, supporting its use as an anaphylaxis marker. The paper does not establish it as the biomarker of choice for defining anaphylaxis or MCAS, or address whether a diagnostic threshold for those conditions was missing. Its threshold discussion concerns baseline tryptase in mastocytosis, not diagnosis of anaphylaxis or MCAS. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Tryptase 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 [12]

    The Introduction (page not provided) says tryptase is concentrated in mast cells and that blood levels correlate with the severity of insect-sting-induced systemic anaphylaxis. This supports its use as a marker of systemic mast-cell activation, but the paper does not establish that it is the most specific and reliable biomarker compared with others, or assess its reliability in daily practice. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • During 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 [12]

    The Introduction says serum or plasma tryptase is measurable during insect-sting systemic anaphylaxis and correlates with reaction severity. The Results describe serum collected 60 minutes after onset of a hypotensive reaction, and the Discussion distinguishes tryptase released by degranulation from tryptase present at baseline. The paper does not show that these patients’ acute levels rose substantially above their own measured baselines. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Schwartz, L. B., Sakai, K., Bradford, T. R., Ren, S., Zweiman, B., Worobec, A. S., & Metcalfe, D. D.
Affiliations
  • Virginia Commonwealth University (US)
  • National Institutes of Health (US)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1995-12-01
Volume
96
Issue
6
Pages
2702-2710
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci118337
PMC
PMC185977
OpenAlex
W2107108810
Cited by
371
References
26
Citations by year
2026: 2 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 13 · 2018: 8 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 16 · 2013: 11 · 2012: 10
FWCI
4.15
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ai014332-21)
  • National Institute of Allergy and Infectious Diseases (AI-14332, AI20487, AI-27517, R01AI027517)
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 › Hematology › Platelet Disorders and Treatments
Keywords
tryptase, beta-tryptase, systemic mastocytosis, mast cells, serum tryptase, anaphylaxis, sandwich immunoassay, diagnostic biomarkers, cutaneous mastocytosis, disease progression monitoring
MeSH terms
Acute Disease, Anaphylaxis, Animals, Antibodies, Monoclonal, Electrophoresis, Polyacrylamide Gel, Humans, Isoenzymes, Kinetics, Mast Cells, Mastocytosis, Recombinant Proteins, Reference Values, Serine Endopeptidases, Blotting, Western, Biomarkers, Mice, Tryptases, Chymases

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