Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell-Mediated Reactions

Purpose of ReviewTo provide an overview on the current understanding of genetic variability in human tryptases and summarize the literature demonstrating the differential impact of mature tryptases on mast cell-mediated reactions and associated clinical phenotypes.Recent FindingsIt is becoming increasingly recognized that tryptase gene composition, and in particular the common genetic trait hereditary alpha-tryptasemia (H alpha T), impacts clinical allergy. H alpha T has consistently been associated with clonal mast cell disorders (MCD) and has also been associated with more frequent anaphylaxis among these patients, and patients in whom no allergic trigger can be found, specifically idiopathic anaphylaxis. Additionally, more severe anaphylaxis among Hymenoptera venom allergy patients has been linked to H alpha T in both retrospective and prospective studies. An increased relative number of alpha-tryptase-encoding gene copies, even in the absence of H alpha T, has also been associated with systemic mastocytosis and has been shown to positively correlate with the severity of mast cell-mediated reactions to vibration and food. These findings may be due to increased generation of alpha/beta-tryptase heterotetramers and differences in their enzymatic activity relative to beta-tryptase homotetramers.SummaryH alpha T is a naturally occurring overexpression model of alpha-tryptase in humans. Increased relative alpha-tryptase expression modifies immediate hypersensitivity symptoms and is associated with more frequent and severe mast cell-mediated reactions, ostensibly due to increased alpha/beta-tryptase heterotetramer production.