tryptase

Tryptase is the most abundant protein in mast cell secretory granules and serves as a specific marker of mast cell activation and degranulation. Unlike histamine, which peaks within minutes and declines rapidly, serum tryptase levels rise more slowly (peaking at 1-2 hours) and remain elevated for several hours (up to 6-24 hours) after a mast cell degranulation event, making it a more practical clinical biomarker for retrospective diagnosis of anaphylaxis. Tryptase is released during IgE-mediated allergic reactions, anaphylaxis (e.g., from insect stings, drug reactions, or food allergies), and in systemic mastocytosis, a clonal mast cell disorder often associated with KIT (CD117) mutations. Baseline tryptase levels are chronically elevated in systemic mastocytosis, while acute spikes above baseline (typically >20% above baseline + 2 ng/mL) support a diagnosis of anaphylaxis. Tryptase also has physiologic roles including activation of protease-activated receptors (PARs), promotion of inflammation, tissue remodeling, and fibrosis. Clinically, serum tryptase is drawn in cases of suspected anaphylaxis (ideally within 1-3 hours of symptom onset) and used as a diagnostic criterion for mastocytosis (WHO criteria includes baseline tryptase >20 ng/mL). It's important to distinguish tryptase elevation from histamine levels, as tryptase offers a longer diagnostic window. Hereditary alpha-tryptasemia, a genetic condition with extra copies of the TPSAB1 gene, can cause chronically elevated tryptase levels independent of mast cell disease, and should be considered in the differential when baseline tryptase is elevated without other mastocytosis features.