Published: January 2026
Medically reviewed by:
Eva Södergren, Sr Manager, Global Medical & Scientific Affairs, Allergy
Recognized as the reference biomarker for mast cell activation, tryptase plays a pivotal role in allergy and hematology diagnostics. Measuring serum tryptase levels helps clinicians understand the mechanisms underlying anaphylaxis, diagnose systemic mastocytosis, and identify mast cell activation syndromes.
What is tryptase?
Tryptase is a tetrameric neutral serine protease and is the most abundant granule protein in mast cells.1,2 Mature tryptase is stored in granules as an active, heparin-stabilized tetramer.1,2 Proforms of α-tryptase and ß-tryptase are continuously released into the circulation and constitute the individual baseline tryptase level in serum or plasma.3,4 Everyone has their own unique baseline level of total tryptase which is normally stable over time.3,4
Tryptase is a marker for mast cell activation and a diagnostic criterion in systemic mastocytosis
Why determine serum tryptase levels?
Tryptase is…
- A useful biomarker in investigation of systemic allergic reaction, as it is released into the circulation during anaphylaxis1,2
- A diagnostic criterion for systemic mastocytosis1,2,5
- A useful screening parameter in mast cell activation and .hereditary alpha-tryptasemia (HαT)5
- An important screening parameter in other myeloid or eosinophilic neoplasms5
Forms and levels of tryptase in health and disease
Tryptase is the most abundant granule protein in mast cells. During IgE-mediated allergic reactions mast cells are activated and release inflammatory mediators including tryptase.5–7 ImmunoCAP™ Tryptase assay measures the total tryptase levels including all forms of α-tryptase and ß-tryptase.8 The table below summarizes the typical tryptase levels in health and disease.
| Mast cells | Total tryptase in health and disease | Tryptase levels | |
| Resting (HαT unlikely)2 | Proforms α-tryptase β-tryptase |
Baseline levels in healthy individuals | 1 – 8 μg/L |
| Hereditary α-tryptasemia2 | Proforms α-tryptase β-tryptase |
Normal range including (asymptomatic) individuals with HaT | 1 – 15 μg/L |
| Hypertryptasemia2 | Elevated baseline levels Underlying mastocytosis |
>15 μg/L | |
| Increased levels3 | Proforms α-tryptase β-tryptase |
Potential systemic mastocytosis or haematological neoplasms | >20 — >>200 μg/L |
| Activated4 | Mature β-tryptase Proforms α-tryptase β-tryptase |
Anaphylactic reaction Severe or fatal systemic reactions |
Transiently elevated from baseline |
ImmunoCAP™ Tryptase assay measures the total tryptase levels including all forms of α-tryptase and ß-tryptase.8
Tryptase in anaphylaxis
Anaphylaxis is a clinical emergency that all healthcare professionals should be aware of!9
Anaphylaxis is a life-threatening reaction characterized by acute onset of symptoms involving different organ systems and requiring immediate medical intervention.9
The symptoms are highly variable:9
- Skin (in ~ 90% cases)
- Respiratory (in ~ 70% cases)
- Cardiovascular (in ~ 70% cases)
- Gastrointestinal (in ~ 50% cases)
- Neurological
Main elicitors:9
- Food
- Drugs
- Venom
Affects children and adults9
Why test for tryptase in anaphylaxis?9-13
- To distinguish between a reaction due to mast cell activation and one with a non-immunological cause
- To predict future severe reactions
To confirm mast cell activation, test tryptase twice5,9
*EAACI recommends a tighter time frame of 30 min to 2 hours, based on the same references.9
Mast cell activation is confirmed if:
∆-tryptase is >20% of the individual’s own baseline tryptase + 2 µg/L
Tryptase in systemic mastocytosis
Mastocytosis: understanding the disease
Mastocytosis is a rare disease characterized by the abnormal accumulation of mast cells in one or several organs, most commonly the skin, bone marrow, and other internal tissues.10,11,14
Mastocytosis are classified into several variants, such as cutaneous mastocytosis (CM)—where mast cell proliferation remains limited to the skin—and systemic mastocytosis (SM), where mast cells infiltrate internal organs.14
To harmonize diagnosis worldwide, the World Health Organization (WHO) has established a set of major and minor diagnostic criteria for SM, which helps clinicians to confirm the diagnosis and to standardize evaluation..14
Although uncommon, the suspicion of mastocytosis often arises in clinical practice when anaphylaxis of an unknown origin and an elevated baseline level of tryptase are observed.10-11,15
The role of tryptase in systemic mastocytosis
Tryptase levels are widely used as a robust screening parameter for patients with suspected SM.16-17
A baseline serum tryptase level exceeding 20 µg/L, when supported by a relevant clinical history, should lead to further investigation for possible mastocytosis.16,18-19
Serum tryptase concentrations vary considerably among the different variants of mastocytosis.17In advanced forms of SM, tryptase also serves as an independent prognostic marker, providing insights into disease burden and progression.17
Importantly, SM is a known risk factor for anaphylaxis — patients diagnosed with SM have a higher likelihood of experiencing recurrent and severe systemic reactions.5
WHO diagnostic criteria for systemic mastocytosis
If at least 1 major and 1 one minor, or at least 3 minor criteria, are met, the diagnosis of systemic mastocytosis can be established.14
| Major criteria1 | Minor criteria1 |
|---|---|
| Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organ(s) (>15 mast cells in aggregate) | a. Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (> 25%) b. C-kit mutation at codon 816 in extracutaneous organ(s). (Activating mutations at codon 816; in most cases, c-kit D816V) c. Mast cells in bone marrow express CD2 and/or CD25 d. Serum total tryptase > 20 μg/L (does not count in patients who have associated hematologic clonal non-mast cell lineage disease-type disease)* |
* When HαT is diagnosed, the BST level should be adjusted.
Hereditary α-tryptasemia
Hereditary α-tryptasemia (HαT) is a common genetic trait caused by the natural overproduction of α-tryptase due to extra copies of the TPSAB1 gene.20
It is a common condition, with a prevalence of about 5.4% in the United States, the United Kingdom and the European Union.21 HαT is also a major cause of elevated basal serum tryptase, accounting for 91% of elevated basal serum tryptase values, with an expected range of 8–50 μg/L.6,22
HαT is over-represented among patients presenting severe hymenoptera venom anaphylaxis or idiopathic anaphylaxis.23 HαT is also more frequent and associated with increased risk of anaphylaxis among individuals with systemic mastocytosis.24
Mast cell activation syndrome (MCAS)
MCAS is a condition in which mast cells release excessive or inappropriate amounts of inflammatory chemicals, such as histamine, cytokines and tryptase, either spontaneously or in response to certain triggers. This excessive release leads to a range of chronic, often multisystemic symptoms.25
| Disorders and syndromes often considered within or related to MCAS | |
|---|---|
| Primary MCAS | Systemic mastocytosis (SM): Characterized by an abnormal proliferation of mast cells Cutaneous mastocytosis (CM): Involves proliferation of mast cells in the skin25 |
| Secondary MCAS | These are caused by underlying allergies, infections, or inflammatory disorders, with mast cell activation occurring secondary to these conditions25 |
| Idiopathic MCAS | Mast cell activation is occurring without a clear underlying cause (like a clonal disorder or secondary trigger).25 |
| Related or Overlapping Disorders25 |
Hereditary alpha-tryptasemia (HαT) Hypermobile Ehlers-Danlos syndrome (hEDS) Postural orthostatic tachycardia syndrome (POTS) |
Key features of MCAS25
Symptoms:
Symptoms vary widely and may affect nearly any organ, most commonly the skin, gastrointestinal tract, cardiovascular, respiratory, and nervous systems.25
Symptoms may include flushing, itching, abdominal pain, diarrhea, headaches, palpitations, and anaphylaxis-like episodes.25
Diagnosis typically involves 3 criteria:25
- Symptoms consistent with mast cell activation in at least two organ systems
- Laboratory evidence of increased mast cell mediators (e.g., elevated serum tryptase, etc.)
- Response to mast cell-targeting treatments
Go further with our expert white paper
To further expand your understanding of tryptase in clinical practice, explore the white paper “The tryptase test—clinical use in immunology, allergy, hematology and dermatology.”
Written by six leading specialists, it provides scientific and clinical insights, along with practical cases and diagnostic algorithms to support day-to-day decision-making.
ImmunoCAP Tryptase assay
| Collecting a sample8 | |
|---|---|
| Calibrator range | 1–200 μg/L |
| Volume needed | 40 μl |
| Specimen collection | Both serum and plasma samples from venous blood can be used |
| Preparation of samples | No need for special procedures when collecting blood or preparing the sample |
See limitations of the procedure as set out in the Directions for Use. ImmunoCAP Tryptase8
Expected values8
A study of 163 self-identified healthy adults (70 males and 93 females, age range 0–68 years) showed a distribution of BST levels with a geometric mean of 3.3 μg/l and a 95th percentile of 8.4 μg/l. The study was performed at our Centre of Excellence in Uppsala, Sweden.
