Clinical Information

Tryptase, a neutral protease, is a dominant protein component of the secretory granules of human mast cells. There are four genes on the human tryptase locus, however, only two of them encode biologically relevant secreted isoforms, designated as alpha- and beta-tryptase.(1) Both secreted isoforms are expressed as inactive proenzymes and spontaneously release from resting mast cells, accounting for measurable basal serum tryptase (BST) concentrations.(1,2) The concentration of protryptases reflect the total number of mast cells within the body but are not an indication of mast cell activation.

Amino acid sequence alterations differentially affect the processing of alpha- and beta-tryptase. Beta-protryptase is efficiently processed to a mature form, which is stored in granules and released as a proteolytically active tetramer that is bound to heparan or chondroitin sulfate proteoglycans. Though highly homologous to beta-tryptase, the two alpha-tryptase isoforms have amino changes that render them either activation resistant or catalytically inactive.  Upon mast cell activation, degranulation releases mature tryptase, which is almost exclusively in the form of beta-tryptase.

During an anaphylactic episode, mast cell granules release tryptase resulting in measurable increases in blood, generally within 30 to 60 minutes.(3) The levels decline under first-order kinetics with half-life of approximately 2 hours. Measurement of tryptase at 1 to 6 hours and at least 24 hours after the anaphylactic episode may be useful in demonstrating a return to baseline concentrations and evaluating the kinetics of the response. Tryptase concentrations may also be increased for a period of time following allergen challenge.

Tryptase is the preferred marker of mast cell involvement in the evaluation of mast cell activation syndrome (MCAS). Elevations exceeding 20% of an individual's baseline + 2 ng/mL fulfill one of the three diagnostic criteria for MCAS.(4) Elevations in basal serum tryptase concentrations are also useful in the evaluation of mastocytosis, a hematologic neoplasm characterize by accumulation of neoplastic mast cells in various organs.(5) Mastocytosis can be categorized as cutaneous and systemic. Cutaneous mastocytosis is generally associated with normal or slightly elevated (11.5-20.0 ng/mL) concentrations of tryptase. In systemic mastocytosis, high concentrations may be observed, with greater than 20 ng+/mL being a minor criterion for the diagnosis of this condition.

Increased concentrations of basal serum tryptase may also be elevated in other conditions, complicating the diagnostic workup of mast cell disorders. Physiological concentrations of BST have been shown to vary among healthy individuals with upper limits of normal ranging from 8.2 to 15 ng/mL in different studies.(6) The source of variation between these studies remains unclear; however, hereditary alpha-tryptasemia (HaT), a genetic trait found in 4% to 7.5% of the western population, has been reported as the most prevalent underlying cause.(6) Individuals with HaT have one or more extra copies of the TSPAB1 gene, which encodes alpha-tryptase, leading to higher concentrations of BST. As most patients harboring the HaT are asymptomatic, the European Competence Network on Mastocytosis and the American Initiative in Mast Cell Diseases have recommended that the normal reference interval for serum tryptase should be 15 ng/mL or lower to avoid unnecessary referrals and workup for mast cell disorders in healthy individuals.(6)