Hereditary α-tryptasemia is associated with anaphylaxis to antibiotics and monoclonal antibodies.

Background: Hereditary α-tryptasemia (HαT)-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: HαT 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). HαT was identified in every individual with elevated BST levels (11.6 to 21.9 ng/mL; n=14) within both cohorts of patients. HαT 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 due to NMBAs, NSAIDs, contrast, chlorhexidine, or other drugs (n=5 of 74; [7%]; P=.02; OR=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 3 ⍺-tryptase copies, the prevalence of severe anaphylaxis was 73% compared to 59% with 1 to 2 ⍺-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 TPSAB1.