ANAPHYLAXIS AND INSECT ALLERGY: Edited by Gianenrico Senna and Mariana CastellsHymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemiaO’Connell, Michael P.; Lyons, Jonathan J.Author Information Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Correspondence to Jonathan J. Lyons, NIH/NIAID/LAD, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD 20892, USA. Tel: +1 301 443 5250; fax: +1 301 451 5563; e-mail: firstname.lastname@example.org Current Opinion in Allergy and Clinical Immunology: October 2020 - Volume 20 - Issue 5 - p 431-437 doi: 10.1097/ACI.0000000000000678 Buy Metrics Abstract Purpose of review To discuss the association between the common dominantly inherited genetic trait hereditary alpha-tryptasemia (HαT) 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. 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. Summary 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.