Hymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia.

Purpose of review To discuss the association between the common dominantly inherited genetic trait hereditary alpha-tryptasemia (H alpha T) and hymenoptera venom-induced anaphylaxis (HVA). Recent findings 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. H alpha T affects an estimated 3-5% of Western populations and is the common cause for elevated BST in these individuals. An association between H alpha T 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 H alpha T fits into this landscape, and review the clinical and mechanistic evidence that supports H alpha T as a modifier of HVA.