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Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond
Open accessAbstract
Tryptase is a serine protease that is predominantly produced by tissue mast cells (MCs) and stored in secretory granules together with other pre-formed mediators. MC activation, degranulation and mediator release contribute to various immunological processes, but also to several specific diseases, such as IgE-dependent allergies and clonal MC disorders. Biologically active tryptase tetramers primarily derive from the two genes TPSB2 (encoding β-tryptase) and TPSAB1 (encoding either α- or β-tryptase). Based on the most common gene copy numbers, three genotypes, 0α:4β, 1α:3β and 2α:2β, were defined as “canonical”. About 4–6% of the general population carry germline TPSAB1-α copy number gains (2α:3β, 3α:2β or more α-extra-copies), resulting in elevated basal serum tryptase levels. This condition has recently been termed hereditary alpha tryptasemia (HαT). Although many carriers of HαT appear to be asymptomatic, a number of more or less specific symptoms have been associated with HαT. Recent studies have revealed a significantly higher HαT prevalence in patients with systemic mastocytosis (SM) and an association with concomitant severe Hymenoptera venom-induced anaphylaxis. Moreover, HαT seems to be more common in idiopathic anaphylaxis and MC activation syndromes (MCAS). Therefore, TPSAB1 genotyping should be included in the diagnostic algorithm in patients with symptomatic SM, severe anaphylaxis or MCAS.
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“However, only α- and β-tryptase are clinically relevant and are the most abundant [7].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [7]
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“heterotetramers have been shown to cleave a subunit of the epidermal growth factor-like module-containing mucin-like hormone receptor-like 2 (EMR2) in vivo thus causing a decrease in the threshold for vibration-induced MC degranulation (16).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [16]
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Metadata
- Authors
- Sprinzl, B., Greiner, G., Uyanik, G., Arock, M., Haferlach, T., Sperr, W. R., Valent, P., & Hoermann, G.
- Affiliations
- Hanusch Hospital (AT)
- Ludwig Boltzmann Institute for Hematology and Oncology (AT)
- Sigmund Freud Privatuniversität Wien (AT)
- Inserm (FR)
- Munich Leukemia Laboratory (Germany) (DE)
- Corresponding author
- Hoermann, Gregor
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-02-28
- Volume
- 22
- Issue
- 5
- Pages
- 2458
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7957558
- OpenAlex
- W3133988438
- Cited by
- 51
- References
- 207
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 11 · 2023: 7 · 2022: 13 · 2021: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Austrian Science Fund (P26079-B13, P32470-684 B, F4701-B20, F4704-B20)
- Medical-Scientific Fund of the Mayor of Vienna (19019)
- 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, hereditary alpha-tryptasemia, TPSAB1, mast cells, systemic mastocytosis, idiopathic anaphylaxis, mast cell activation syndrome, gene copy number, genetic control, serum tryptase
- MeSH terms
- Animals, Humans, Mast Cells, Mastocytosis, Gene Expression Regulation, Enzymologic, Genetic Diseases, Inborn, Tryptases
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