ArticleThe Journal of experimental medicine2019
Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 117 citations in OpenAlex.
- Hypersensitivity Reactions to Biologics: Advances in Diagnosis and Management.Current allergy and asthma reports · 2026Review
- Extended multisystem manifestations of hereditary α-tryptasemia in an allergy center cohort.The journal of allergy and clinical immunology. Global · 2026Article
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Hereditary Alpha-Tryptasemia (HαT) as a Risk Modifier for Severe Anaphylaxis.Immunology and allergy clinics of North America · 2026Review
- Sexual Dimorphism in Allergic and Mast Cell-Associated Diseases.Clinical reviews in allergy & immunology · 2026Review
- Legends of Allergy-Lawrence B. Schwartz.Allergy · 2026Article
- Hereditary Alpha-Tryptasemia and Mastocytosis: What We Know and What We Need To Learn.Current allergy and asthma reports · 2026Review
- Hereditary α-tryptasemia; a review of mechanisms linking α-tryptase gene dosage to intestinal homeostasis and immunopathology.Frontiers in allergy · 2026Review
- MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia.medRxiv : the preprint server for health sciences · 2025Article
- Evolution of mast cell research associated with the Laboratory of Allergic Diseases, 1985-2022: Summary of the 2023 NIAID Symposium.The Journal of allergy and clinical immunology · 2025Review
- Emergency Monitoring Following A Diagnosis of Anaphylaxis.Current allergy and asthma reports · 2025Review
- Towards a Multi-omics Understanding of Anaphylaxis: Insights into Pathogenesis and Biomarker Identification.Clinical reviews in allergy & immunology · 2025Review
- Neurogenic Inflammation in Allergic Contact Dermatitis.Biomedicines · 2025Review
- First demonstration of implication of hereditary alpha-tryptasaemia in vasospastic angina: a case report.European heart journal. Case reports · 2025Article
- Mast Cells at the Crossroads of Hypersensitivity Reactions and Neurogenic Inflammation.International journal of molecular sciences · 2025Review
- Defining "Normal" basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis.Frontiers in allergy · 2025Review
- Cold-induced anaphylaxis: new insights into clinical and genetic characteristics.Frontiers in immunology · 2025Article
- Utility of tryptase genotyping in the screening, diagnosis, and management of systemic mastocytosis.Frontiers in allergy · 2025Review
- Hereditary alpha tryptasemia and food allergy.Frontiers in allergy · 2025Review
- Hereditary alpha-tryptasemia and monoclonal mast cell disorders.Frontiers in allergy · 2025Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
Both α-tryptase and β-tryptase are preferentially expressed by human mast cells, but the purpose of α-tryptase is enigmatic, because its tetramers lack protease activity, whereas β-tryptase tetramers are active proteases. The monogenic disorder called hereditary α-tryptasemia, due to increased α-tryptase gene copies and protein expression, presents with clinical features such as vibratory urticaria and dysautonomia. We show that heterotetramers composed of 2α- and 2β-tryptase protomers (α/β-tryptase) form naturally in individuals who express α-tryptase. α/β-Tryptase, but not homotetramer, activates protease-activated receptor-2 (PAR2), which is expressed on cell types such as smooth muscle, neurons, and endothelium. Also, only α/β-tryptase makes mast cells susceptible to vibration-triggered degranulation by cleaving the α subunit of the EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) mechanosensory receptor. Allosteric effects of α-tryptase protomers on neighboring β-tryptase protomers likely result in the novel substrate repertoire of α/β-tryptase tetramers that in turn cause some of the clinical features of hereditary α-tryptasemia and of other disorders involving mast cells.
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