Hereditary α-tryptasemia is associated with anaphylaxis to antibiotics and monoclonal antibodiesKorošec, Peter (Avtor) Lyons, Jonathan J. (Avtor) Svetina, Manca (Avtor) Koudová, Monika (Avtor) Bittóová, Martina (Avtor) Zidarn, Mihaela (Avtor) Sedláčková, Lenka (Avtor) Rijavec, Matija (Avtor) Kopač, Peter (Avtor) immunologydrug allergyanaphylaxisantibioticsmonoclonal antibodiesα-tryptasehereditary α-tryptasemiaBackground Hereditary α-tryptasemia, a genetic trait caused by increased α-tryptase copy number, is associated with idiopathic and venom anaphylaxis. Objective We aimed to determine the impact of tryptase genotypes on drug-induced anaphylaxis. Methods A prospective discovery cohort of 99 patients from a referral center in Slovenia with acute anaphylaxis to drugs underwent tryptase genotyping by droplet digital PCR. For validation, we included a cohort of 26 patients from the Czech Republic. Associated inciting agents and the severity of the reactions were subsequently examined. Results Hereditary α-tryptasemia was associated with drug-induced anaphylaxis with a prevalence of 13% (n = 13 of 99) in the discovery cohort and 15% in the validation cohort (n = 4 of 26). Hereditary α-tryptasemia was identified in every individual with elevated basal serum tryptase levels (11.6-21.9 ng/mL; n = 14) within both cohorts of patients. Hereditary α-tryptasemia was more prevalent in individuals with antibiotic- or mAb-induced anaphylaxis in both the discovery and validation cohorts (n = 13 of 51; 26%) compared to those with anaphylaxis resulting from neuromuscular blocking agents, nonsteroidal anti-inflammatory drugs, contrast, chlorhexidine, or other drugs (n = 5 of 74; 7%; P = .02; odds ratio = 4.1; 95% CI, 1.3-11.1). Overall, we found fewer individuals with no ⍺-tryptase than in the general population, and there was a trend for subjects with more ⍺-tryptase copies to have more severe reactions. Thus, among subjects with three ⍺-tryptase copies, the prevalence of severe anaphylaxis was 73%, compared with 59% with one to two ⍺-tryptase copies and 58% for subjects without ⍺-tryptase. Conclusions Risk for anaphylaxis to antibiotics and biologics is associated with inherited differences in α-tryptase–encoding copies at Tryptase α/β1 .Elsevier, 2013-20252025-06-18 14:01:59Neznano22721The journal of allergy and clinical immunology. In practicesl© 2025 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).