Alphatryptase

Alphatryptase is a serine protease of the tryptase family produced by mast cells. It is one of the two major human tryptases, the other being beta-tryptase. The alpha form is encoded mainly by the TPSAB1 gene, which resides on chromosome 16p13.3, and copy number variation at this locus can give rise to hereditary alpha-tryptasemia (HαT). In contrast, beta-tryptase is encoded by a related gene and is typically the more abundant and enzymatically active form released during mast cell activation.

Biochemically, tryptases are secreted as inactive zymogens and assemble into active serine protease tetramers. Alpha- and beta-tryptase subunits can form homotetramers or mixed tetramers, and the catalytic activity of alpha-tryptase differs from that of beta-tryptase. Alpha-tryptase is generally considered less enzymatically active than beta-tryptase, though tetramer composition can influence overall activity. Both forms are stored in mast cell granules and released upon degranulation, contributing to inflammatory and vasodilatory responses.

Genetically, HαT results from increased copies of TPSAB1 encoding alpha-tryptase, leading to higher baseline serum tryptase levels in some individuals. The clinical significance of HαT varies; many carriers are asymptomatic, while others report a range of symptoms that may overlap with mast cell–related disorders, such as generalized malaise, pain, or hypersensitivity phenomena.

Diagnosis typically involves serum tryptase measurement and genetic analysis of TPSAB1 copy number. Management is individualized and focuses on addressing any mast cell–associated symptoms rather than the alphatryptase itself.