Tryptase is an enzyme primarily stored within mast cells, immune cells distributed throughout the body (e.g., skin, airways, digestive tract). Normally, this enzyme is present in the bloodstream at very low, stable concentrations. When mast cells are activated, they rapidly release stored chemicals, including tryptase and histamine, into the circulation. An elevated level of tryptase indicates significant mast cell activation. Understanding the causes of high tryptase levels helps distinguish between acute, temporary immune responses and persistent, underlying health conditions.
The Function of Mast Cells and Measuring Tryptase
Mast cells play a role in immediate allergic reactions and inflammation. They contain granules filled with chemical mediators that are released upon encountering a trigger, such as an allergen or pathogen. The release of these mediators, including tryptase, causes symptoms like flushing, itching, and difficulty breathing.
Measuring tryptase involves two distinct approaches. Peak/Acute Tryptase is measured shortly after a suspected event (ideally within one to two hours of symptom onset) to confirm recent mast cell degranulation. This acute level is compared to the Baseline Tryptase level, which represents the individual’s typical, steady-state concentration. The baseline sample must be collected at least 24 hours after an acute reaction has completely resolved to accurately reflect the normal state.
Acute and Immediate Triggers (Anaphylaxis)
The most common reason for a sudden, temporary spike in tryptase is anaphylaxis, a severe systemic allergic reaction. During anaphylaxis, a trigger causes widespread, rapid degranulation of mast cells throughout the body. This release of mediators leads to life-threatening symptoms, such as circulatory collapse and airway obstruction.
The resulting tryptase elevation is rapid, often peaking between one and two hours after the reaction begins. Common triggers include foods, insect stings, and medications. In the hospital setting, drugs used during surgery (e.g., neuromuscular blocking agents or certain antibiotics) are also known to cause anaphylaxis and a corresponding tryptase spike.
This acute elevation is transient, typically returning to the individual’s baseline within 12 to 24 hours. A significant rise, defined by the “20+2 rule” (a 20% increase over baseline plus 2 ng/mL), confirms that mast cell activation caused the acute symptoms. Testing for this acute elevation is important for confirming anaphylaxis, especially when the cause of a patient’s collapse is uncertain.
Chronic Conditions Causing Persistent Elevation
In contrast to acute spikes, a persistently elevated baseline tryptase level indicates a chronic condition, often suggesting an underlying issue with the mast cell population. A baseline level above 11.4 ng/mL is considered elevated, and a level above 20 ng/mL suggests a clonal mast cell disorder. This elevation can be caused by an increased number of mast cells or a genetic predisposition affecting enzyme production.
The most recognized cause of persistently high tryptase is systemic mastocytosis (SM), characterized by the abnormal growth and accumulation of mast cells in various tissues (e.g., bone marrow, spleen, and liver). The increased number of mast cells, known as mast cell burden, correlates with the elevated baseline tryptase level. Most SM cases involve the D816V mutation in the KIT gene, which leads to the uncontrolled proliferation and survival of these cells.
Another cause of chronic elevation is Hereditary Alpha-Tryptasemia (HAT), a common genetic trait affecting up to 6% of the general population. Individuals with HAT have extra copies of the TPSAB1 gene, which codes for alpha-tryptase, leading to higher baseline levels (often above 8 ng/mL). The elevated tryptase in HAT is due to increased enzyme production, not necessarily an increase in mast cell numbers or chronic activation. HAT can be asymptomatic, but it is associated with an increased risk of severe anaphylaxis and can worsen the symptoms of other mast cell-related conditions. Less common causes of persistent elevation include certain hematologic malignancies, such as myelodysplastic syndromes, and chronic kidney disease.
Diagnostic Procedures Following High Tryptase
Once a high baseline tryptase level is detected, a physician typically initiates specialized procedures to determine the cause. If systemic mastocytosis is suspected, a bone marrow biopsy is often performed to look for abnormal collections of mast cells (the major diagnostic criterion). The bone marrow sample also allows for molecular testing to check for the KIT D816V mutation, a key minor criterion for diagnosing mastocytosis.
If the baseline tryptase is consistently elevated (especially above 8 ng/mL), genetic testing for Hereditary Alpha-Tryptasemia is often recommended. This test identifies extra copies of the TPSAB1 gene to confirm the genetic predisposition. Tracking the baseline level over time is important for monitoring the stability or progression of any underlying mast cell disorder.