Hereditary α-tryptasemia is Associated With Anaphylaxis to Antibiotics and Monoclonal Antibodies.

Abstract

Hereditary α-tryptasemia, a genetic trait caused by increased α-tryptase copy number, is associated with idiopathic and venom anaphylaxis. We aimed to determine the impact of tryptase genotypes on drug-induced anaphylaxis. 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. 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. Risk for anaphylaxis to antibiotics and biologics is associated with inherited differences in α-tryptase-encoding copies at Tryptase α/β1.