Differential mast cell mediators in systemic mastocytosis and hereditary α-tryptasemia
Abstract
Background Patients with systemic mastocytosis often have symptoms of mast cell activation, which is associated with elevated levels of urinary mast cell mediator metabolites. Patients with hereditary α-tryptasemia (HαT) may present with symptoms of mast cell activation. Whether levels of mast cell mediators are elevated in this patient population is not known. Objective The purpose of this study was to determine whether patients with HαT and symptoms of mast cell activation have elevated levels of urinary mediators and compare the levels with those in patients with systemic mastocytosis. Methods We retrospectively analyzed mast cell mediators in 63 patients with a confirmed diagnosis of HαT, 20 patients with a confirmed diagnosis of indolent systemic mastocytosis (ISM), and 23 healthy controls. All patients were referred to the Brigham and Women's Hospital Mastocytosis Center or the Mayo Clinic for evaluation of mast cell activation disorders. Results Our population was predominantly female (85.7%) with an average age of 53.8 years. The average baseline serum tryptase level was significantly higher in patients with ISM than in those with HαT (65.9 vs 19.3 ng/mL [P Conclusion Patients with symptomatic HαT do not have elevations of mast cell urinary metabolites, suggesting that granule- and membrane-derived mediators may not drive symptoms in HαT.
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Other mediators such as platelet-activating factor (PAF), prostaglandin D2, leukotriene E4, histamine, or other cytokines might be more sensitive in patients with food-induced anaphylaxis.
“It is possible that other mediators such as platelet-activating factor (PAF), prostaglandin D2, leukotriene E4, histamine, or other cytokines might be more sensitive in these patients [34,35,36,37].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [34]
Urinary metabolites of mediators (methylhistamine, prostaglandin F2-alpha, and leukotriene E4) are higher in systemic mastocytosis cases than in subjects with symptomatic hereditary alpha-tryptasemia.
“The study showed that the urinary metabolites of mediators (i.e., methylhistamine, prostaglandin F2-alpha, and leukotriene E4) were higher in SM cases than in subjects with symptomatic HαT.”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [70]
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- Authors
- Giannetti, M. P., Godwin, G., Weller, E., Butterfield, J. H., & Castells, M.
- Affiliations
- Brigham and Women's Hospital (US)
- Mayo Clinic (US)
- Corresponding author
- Giannetti, Matthew P.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 150
- Issue
- 5
- Pages
- 1225-1227
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W4229365737
- Cited by
- 25
- References
- 5
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 4 · 2023: 5
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- hereditary alpha-tryptasemia, systemic mastocytosis, indolent systemic mastocytosis, mast cell activation, N-methylhistamine, serum tryptase, mast cell mediators
- MeSH terms
- Mast Cell Activation Syndrome, Female, Humans, Male, Mast Cells, Mastocytosis, Middle Aged, Retrospective Studies, Mastocytosis, Systemic, Tryptases
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