Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis
Open accessAbstract
The association between Hymenoptera venom-triggered anaphylaxis (HVA) and clonal mast cell-related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom-triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from 'how many patients with cMCD have anaphylaxis?' to 'how many patients with anaphylaxis have cMCD?'. The discovery of hereditary α-tryptasemia (HαT)-a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene-, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk = 2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β -tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell-related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.
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HαT seems to be a disease-modifying trait in anaphylaxis and PMCD.
“However, it seems to be a disease-modifying trait in anaphylaxis and PMCD [19,20,21].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [20]
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Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
Sorted by citations
Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders
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- Authors
- Kačar, M., Rijavec, M., Šelb, J., & Korošec, P.
- Affiliations
- University of Ljubljana (SI)
- Corresponding author
- Korošec, Peter
- Venue
- Clinical & Experimental Allergy
- Publisher
- Wiley
- Published
- 2023-01-18
- Volume
- 53
- Issue
- 4
- Pages
- 392-404
- ISSN
- 0954-7894 (ISSN-L)
- 1365-2222
- OpenAlex
- W4317481693
- Cited by
- 37
- References
- 110
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 8
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical & Experimental Allergy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repository of the University of Ljubljana (University of Ljubljana) (submittedVersion, cc-by-nc-nd)
- Funders
- Javna Agencija za Raziskovalno Dejavnost RS
- 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 › Drug-Induced Adverse Reactions
- Keywords
- clonal mast cell disorders, hereditary alpha-tryptasemia, anaphylaxis, KIT D816V mutation, idiopathic anaphylaxis, food allergy, drug hypersensitivity, risk factors
- MeSH terms
- Mast Cell Activation Syndrome, Anaphylaxis, Arthropod Venoms, Humans, Mast Cells, Mastocytosis, Risk Factors, Tryptases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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