tryptases

Tryptases are a family of serine proteases stored in the secretory granules of mast cells and, to a lesser extent, basophils. They are released during mast cell activation and contribute to inflammatory and allergic responses, including anaphylaxis. In humans, the two best characterized isoforms are alpha-tryptase and beta-tryptase, with beta-tryptase generally more enzymatically active.

Biochemically, tryptases are produced as proenzymes that are secreted into tissues and blood mainly as tetrameric enzymes. Their functional activity is stabilized by heparin and other glycosaminoglycans present in mast cell granules, and fully active tetramers form after secretion. The two main isoforms differ in expression patterns and activity, and additional minor variants exist due to genetic variation in the tryptase gene cluster.

Genetically, tryptases are encoded by a cluster on chromosome 16 that includes TPSAB1 and TPSB2, among others. Variation in copy number and expression gives rise to different individual baselines. Hereditary alpha-tryptasemia is a condition caused by inheritance of TPSAB1 copy-number variations that elevates baseline tryptase without necessarily causing overt disease, though it can be associated with symptoms such as mast cell–related discomfort in some individuals.

Clinical relevance centers on measurement of serum tryptase as a biomarker of mast cell activation. In anaphylaxis, tryptase levels typically rise within 1–2 hours after onset and return toward baseline within 24–48 hours. A persistent elevation in baseline tryptase can suggest a clonal mast cell disorder such as systemic mastocytosis, while interpretations must consider timing and clinical context.