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Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis
Open accessAbstract
Mastocytosis is a hematopoietic neoplasm characterized by expansion of KIT D816V-mutated clonal mast cells in various organs and severe or even life-threatening anaphylactic reactions. Recently, hereditary α-tryptasemia (HαT) has been described as a common genetic trait with increased copy numbers of the α-tryptase encoding gene, TPSAB1, and associated with an increased basal serum tryptase level and a risk of mast cell activation. The purpose of our study was to elucidate the clinical relevance of HαT in patients with mastocytosis. TPSAB1 germline copy number variants were assessed by digital polymerase chain reaction in 180 mastocytosis patients, 180 sex-matched control subjects, 720 patients with other myeloid neoplasms, and 61 additional mastocytosis patients of an independent validation cohort. α-Tryptase encoding TPSAB1 copy number gains, compatible with HαT, were identified in 17.2% of mastocytosis patients and 4.4% of the control population (P < .001). Patients with HαT exhibited higher tryptase levels than patients without HαT (median tryptase in HαT+ cases: 49.6 ng/mL vs HαT− cases: 34.5 ng/mL, P = .004) independent of the mast cell burden. Hymenoptera venom hypersensitivity reactions and severe cardiovascular mediator-related symptoms/anaphylaxis were by far more frequently observed in mastocytosis patients with HαT than in those without HαT. Results were confirmed in an independent validation cohort. The high prevalence of HαT in mastocytosis hints at a potential pathogenic role of germline α-tryptase encoding TPSAB1 copy number gains in disease evolution. Together, our data suggest that HαT is a novel emerging robust biomarker in mastocytosis that is useful for determining the individual patient´s risk of developing severe anaphylaxis.
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“There is a consensus that HαT is a risk modifier of severe anaphylaxis [21,48,49,50,51,52,53].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [51]
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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“In patients with systemic mastocytosis (SM), the risk for developing severe or even life-threatening anaphylaxis is high, especially when a concomitant IgE-dependent allergy or the genetic trait Hereditary a -tryptasemia (H a T) is present.”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [25]
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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“However, an approximately two to three times higher prevalence of H a T has been reported in two large cohorts of SM patients 25,129 ; also, H a T concurrently occurring with MCAS has been reported. 130,131”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [25]
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“Further, H a T may be associated with an increased severity of anaphylactic reactions and other mediator-induced symptoms in patients with mastocytosis and venom allergy. 25,129”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [25]
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“in patients with SM, where it can reach up to 12%–20% (17, 19, 22, 23).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [22]
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“HαT is enriched in patients with SM,42,43 in Hymenoptera-allergic patients with severe anaphylaxis,44,45 and in patients with idiopathic anaphylaxis.42,43,45,46”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [43]
In the citing paper
“Furthermore, MCAS has been reported in patients with hereditary a-tryptasemia (HaT), an autosomal dominant genetic trait caused by an increased copy-number of the atryptase gene TPSAB1, resulting in increased baseline serum tryptase levels.7,8”
From Low Prevalence of Idiopathic Mast Cell Activation Syndrome Among 703 Patients With Suspected Mast Cell Disorders (2024) · cites this paper as [7]
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Metadata
- Authors
- Greiner, G., Sprinzl, B., Górska, A., Ratzinger, F., Gurbisz, M., Witzeneder, N., Schmetterer, K. G., Gisslinger, B., Uyanik, G., Hadzijusufovic, E., Esterbauer, H., Gleixner, K. V., Krauth, M. T., Pfeilstöcker, M., Keil, F., Gisslinger, H., Nedoszytko, B., Niedoszytko, M., Sperr, W. R., Valent, P., & Hoermann, G.
- Affiliations
- Ludwig Boltzmann Institute for Hematology and Oncology (AT)
- Hanusch Hospital (AT)
- Gdańsk Medical University (PL)
- Ihr Labor, Medical Diagnostic Laboratories, Vienna, Austria;
- Medical University of Vienna (AT)
- Sigmund Freud Privatuniversität Wien (AT)
- University of Veterinary Medicine Vienna (AT)
- Department of Dermatology, Medical University of Gdańsk, Gdańsk, Poland;
- Innsbruck Medical University (AT)
- Corresponding author
- Hoermann, Gregor
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2021-01-14
- Volume
- 137
- Issue
- 2
- Pages
- 238-247
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC7116780
- OpenAlex
- W3048592971
- Cited by
- 189
- References
- 59
- Citations by year
- 2026: 24 · 2025: 31 · 2024: 28 · 2023: 29 · 2022: 33 · 2021: 40
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- hereditary alpha-tryptasemia, mastocytosis, TPSAB1, copy number gain, genetic biomarkers, anaphylaxis, KIT D816V mutation, mast cell activation, myeloid neoplasms
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Genetic Markers, Humans, Male, Mastocytosis, Middle Aged, Tryptases, Young Adult, DNA Copy Number Variations
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