Elevated Basal Serum Tryptase: Disease Distribution and Variability in a Regional Health System
Open accessAbstract
Background Hereditary-alpha tryptasemia (HαT) is the most common etiology for elevated basal serum tryptase (BST). However, the utility of tryptase genotyping of individuals with elevated BST in general clinical practice remains undefined. Moreover, studies showing associations between elevated BST and chronic kidney disease (CKD), myelodysplastic syndrome (MDS), rheumatoid arthritis, or eosinophilic esophagitis did not include tryptase genotyping.Objective To determine the utility of tryptase genotyping among individuals with moderate elevations in BST at a regional health system.Methods Clinical and laboratory data from 109 subjects with basal tryptase values of 7.5 ng/mL or greater who were tested for HαT or had a disorder previously linked to elevated BST were collected retrospectively by chart review.Results Fifty-eight subjects had elevated BST defined as 11.5 ng/mL or greater. HαT was found in 63.8% (n = 37), 12.1% (n = 7) had CKD, and 20.7% (n = 12) had clonal myeloid disorders. A total of 6.9% (n = 4) with elevated BST had negative testing for HαT, CKD, and myeloid neoplasms. Two subjects with CKD, 1 subject with MDS, and 1 with myeloid hypereosinophilic syndrome had negative testing for HαT. Among subjects with elevated BST and more than 1 tryptase measurement, 41.5% (n = 22) had BST variability that exceeded the 20% plus 2 formula. Increased BST variability was found in subjects with HαT, all forms of mastocytosis, CKD, MDS, and those with no associated diagnosis.Conclusions HαT, CKD, and clonal myeloid disorders or a combination of the 3 constitute approximately 90% of individuals with elevated BST in clinical practice. Myeloid neoplasms were over-represented in this cohort relative to population prevalence data suggesting tryptase measurement selection bias by clinicians or higher prevalence. Elevated BST is associated with increased tryptase variability, regardless of etiology.
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Serum baseline tryptase levels can be elevated secondary to other numerous non-MC related conditions, the most common being chronic kidney disease.
“Finally, serum bST levels can be elevated secondary to other numerous non-MC related conditions, the most common being chronic kidney disease (CKD) [22].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [22]
The Results (page unavailable) report an independent association between elevated basal serum tryptase and CKD, supporting CKD as a non–mast-cell-related explanation. But the Abstract Background calls hereditary alpha-tryptasemia the most common etiology, and the Discussion reports CKD in 12.1% of patients with elevated levels; the paper does not establish CKD as the most common of all non–mast-cell-related conditions. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHαT is the cause of an elevated baseline serum tryptase in about 90% of patients and is found in up to 6% of the general population.
“It is the cause of an elevated bST in about 90% of patients and is found in up to 6% of the general population [8,22].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [22]
The Discussion says HαT is present in approximately 5% of populations with European background, consistent with 'up to 6%' but narrower than a claim about the general population. It reports HαT in 63.8% of the studied patients with elevated BST; approximately 90% is the combined figure for HαT, myeloid neoplasms, and CKD, not HαT alone. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe prevalence of HαT is estimated at around 5% of the general population.
“The prevalence of HαT is estimated at around 5% of the general population.”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [20]
The Discussion reports HαT in approximately 5% of populations with European background. That supports the estimate, but not its extension to the general population without that qualifier. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBST normal values have been established in the range of 1 to 11.5 ng/ml.
“BST normal values have been established in the range of 1 to 11.5 ng/ml (20, 24)”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [20]
The Introduction (page unavailable) treats BST below 11.5 ng/mL as below the elevated threshold, and the Results call 7.5 to <11.5 ng/mL “high-normal.” Our copy does not establish 1 ng/mL as the lower limit of a normal range, so it supports only the upper end of the claimed range. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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Madsen, A. T., Kristiansen, H. P., & Winther‐Larsen, A. (2023) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2023-0606 · Cited by 7 · see citing works
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Puxkandl, V., Aigner, S., Hoetzenecker, W., & Altrichter, S. (2024) · Frontiers in Allergy · doi:10.3389/falgy.2024.1461359 · Cited by 6 · see citing works
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Mastozytose – eine häufig unerkannte Erkrankung
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Mast Cell Activation Syndrome and Mimickers
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- Authors
- Waters, A. M., Park, H. J., Weskamp, A. L., Mateja, A., Kachur, M. E., Lyons, J. J., Rosen, B. J., & Boggs, N. A.
- Affiliations
- Walter Reed National Military Medical Center (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institutes of Health (US)
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Boggs, Nathan A.
- ORCID
- Venue
- The Journal of Allergy and Clinical Immunology In Practice
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 10
- Issue
- 9
- Pages
- 2424-2435.e5
- ISSN
- 2213-2198 (ISSN-L)
- PMC
- PMC9273808
- OpenAlex
- W4206391175
- Cited by
- 46
- References
- 51
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 12 · 2022: 8
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Allergy and Clinical Immunology In Practice (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (75N910D00024, 75N91019F00130)
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Rheumatology › Eosinophilic Disorders and Syndromes
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Keywords
- hereditary alpha-tryptasemia, chronic kidney disease, myelodysplastic syndrome, mastocytosis, eosinophilic esophagitis, rheumatoid arthritis, disease distribution
- MeSH terms
- Humans, Mast Cells, Mastocytosis, Myelodysplastic Syndromes, Retrospective Studies, Renal Insufficiency, Chronic, Tryptases
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