Hymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia

To discuss the association between the common dominantly inherited genetic trait hereditary alpha-tryptasemia (HαT) and hymenoptera venom-induced anaphylaxis (HVA).

Elevated BST has been correlated with more severe systemic anaphylaxis in humans in a number of settings - most notably in HVA. Clonal mast cell disease, in particular, systemic mastocytosis, is frequently associated with elevated BST, and is a major risk factor for severe HVA. However, clonal mast cell diseases are believed to be rare, whereas HVA is relatively more common. HαT affects an estimated 3-5% of Western populations and is the common cause for elevated BST in these individuals. An association between HαT and severe HVA, as well as clonal mast cell disease has recently been demonstrated wherein this trait modifies reaction severity in venom allergic individuals. A mechanism underlying this association has been proposed through the identification of naturally occurring heterotetrameric tryptases and characterization of their unique physical attributes.

Here we discuss the long-standing association between elevated BST and HVA severity, how HαT fits into this landscape, and review the clinical and mechanistic evidence that supports HαT as a modifier of HVA.