Inherited and acquired determinants of serum tryptase levels in humans
Open accessAbstract
Objective To aid the clinician in correctly interpreting serum tryptase levels.Data sources Primary peer-reviewed literature.Study selections Clinical and basic science peer-reviewed studies characterizing the genetic and physiological bases for tryptase generation, secretion, and elevation, including those describing serum tryptase levels in population-based cohort studies.Results Clinically measured basal serum tryptase (BST) consists of ostensibly inactive alpha- and beta-tryptase precursors. The autosomal dominant genetic trait hereditary alpha-tryptasemia is the most often cause for elevated BST levels, with other acquired causes, such as renal failure and clonal myeloid diseases being far less common. Acute increases in serum tryptase levels resulting from release of mature tryptase from secretory granules is specific to mast cell degranulation but is not detected in all cases of systemic anaphylaxis.Conclusion Understanding the differences and distinguishing between acute increases in serum tryptase and chronic elevations in BST owing to inherited or acquired conditions is critical in the correct interpretation of this useful clinical biomarker.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Resting mast cells constitutively secrete monomeric pro-tryptase.
“Resting MCs constitutively secrete monomeric pro-tryptase [8].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [8]
The section “Basal Serum Tryptase Consists of Enzymatically Inactive Propeptides” (page not available) says that pro-tryptases are released constitutively, in contrast to mature tryptases released after mast-cell activation. It does not state that the secreted pro-tryptases are monomeric. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe most common reason for elevated baseline serum tryptase is HαT (91%), followed by chronic renal failure (7%) and hematologic malignancies and mastocytosis (1%).
“The most common reason is HαT (91%), followed by chronic renal failure (7%) and hematologic malignancies and mastocytosis (1%) [8,19].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [8]
The Introduction and Conclusion identify HαT as the most common cause of elevated baseline serum tryptase; the Conclusion says advanced or end-stage renal disease is approximately 13-fold less common. The Acquired Causes section also associates mastocytosis and other myeloid neoplasms with elevated levels. Our copy does not give the claimed 91%, 7%, and 1% breakdown, and specifies advanced kidney disease rather than chronic renal failure generally. (LLM, conf=0.86)
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 [8]
The section “Hereditary Alpha-Tryptasemia: the Most Common Cause for BST Elevation” reports that HαT accounts for an estimated 91% of elevated BST among individuals in the general population, supporting the ‘about 90%’ figure. It says approximately 6% of the general population has elevated BST—not that 6% has HαT—and does not establish the same proportion specifically among patients. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHelminthic infections, hematological malignancies, cardiovascular disease, (nummular) eczema, or rare genetic mutations (e.g., GATA2 or PLAID) can cause elevated baseline serum tryptase.
“Moreover, obesity can be a cause of elevated bST [77], as well as helminthic infections, hematological malignancies, cardiovascular disease, (nummular) eczema, or rare genetic mutations (e.g., GATA2 or PLAID) [8,78,79].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [8]
The sections on hereditary alpha-tryptasemia and acquired causes of BST elevation associate elevated baseline serum tryptase with GATA2 haploinsufficiency, PLAID, and clonal myeloid malignancies (page numbers unavailable). The passages found do not support helminthic infections, cardiovascular disease, or (nummular) eczema as causes. Obesity has a separate citation in the citing sentence and is not assessed here. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe growing knowledge of HαT, a germline condition causing increase in BST, has not fully elucidated clinical consequences.
“growing knowledge of hereditary alpha-tryptasemia (HαT), a germline condition causing increase in BST with not fully elucidated clinical consequences (4–6).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [5]
The section “Hereditary Alpha-Tryptasemia: the Most Common Cause for BST Elevation” (page not provided) identifies HαT as an autosomal dominant genetic trait caused by increased TPSAB1 copy number and links it to higher BST. The paper describes some associated clinical findings, but the passages reviewed do not say that HαT’s clinical consequences remain incompletely elucidated. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Three other methods of correction for BST according to HαT genotype have been proposed.
“In addition to this, three other methods of correction have been proposed (5, 13, 23) (Table 2).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [5]
The section on Hereditary Alpha-Tryptasemia reports that each additional TPSAB1 copy raises BST by approximately 9 ng/mL, but it does not propose a method for correcting BST by genotype. Searches for corrected or adjusted BST and proposed correction methods found no passage describing such a method, let alone three. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 76 · Cited by 52
- Authors
- Lyons, J. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lyons, Jonathan J.
- ORCID
- Lyons, Jonathan J.
- Venue
- Annals of Allergy, Asthma & Immunology
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 127
- Issue
- 4
- Pages
- 420-426
- ISSN
- 1081-1206 (ISSN-L)
- PMC
- PMC8919864
- OpenAlex
- W3174044695
- Cited by
- 52
- References
- 76
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 5 · 2023: 8 · 2022: 13 · 2021: 3
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Allergy Asthma & Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- Government of South Australia
- National Institutes of Health
- 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 › Physiology › Asthma and respiratory diseases
- Keywords
- serum tryptase, hereditary alpha-tryptasemia, mast cell degranulation, systemic anaphylaxis, renal failure, biomarker interpretation
- MeSH terms
- Anaphylaxis, Enzyme Precursors, Humans, Mast Cells, Mastocytosis, Biomarkers, Cell Degranulation, Renal Insufficiency, 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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
