Tryptase Locus Variation Contributes to Normal-Range Basal Serum Tryptase Variability and Is Associated With Anaphylaxis.

Authors

Manca Svetina, Jonathan J Lyons, Peter Kopač, Julij Šelb, Mitja Košnik, Matija Rijavec, Peter Korošec

Published in

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. Oct 07, 2026. Epub Oct 07, 2026.

Abstract

Increased basal serum tryptase level (BST) is associated with anaphylaxis. In the absence of clonal mast cell disease and hereditary α-tryptasemia (HαT), the contribution of the tryptase locus variation to BST and anaphylaxis remains undefined.
To determine the impact of tryptase locus variation on BST and anaphylaxis.
Individuals with systemic Hymenoptera venom allergic reactions, large local reactions and asymptomatic sensitization underwent a novel ddPCR-based tryptase genotyping to quantify active tryptase alleles. Individuals positive for KIT p.D816V or HαT were excluded.
The cohort consisted of 295 individuals with systemic reactions, 140 with large local reactions, and 29 asymptomatically sensitized individuals. Active tryptase allele number, excluding the inactive βIIIFS allele, correlated with BST levels (r = 0.34, p < 0.0001); all BST values were within the normal range. Patients with systemic reactions had higher BST compared with those with large local reactions and asymptomatic sensitization (median, 4.5 ng/mL vs. 3.5 ng/mL; p < 0.0001). Individuals carrying four active β-tryptase alleles were less likely to experience anaphylaxis than those carrying two or three active β-tryptase alleles (26.7% vs. 42.3%; p = 0.024). A trend towards more severe reactions was observed in individuals carrying α-tryptase allele together with a higher number of active β-tryptase alleles.
Variation at the tryptase locus explains differences in BST levels within the normal range. Four active β-tryptase alleles were associated with a lower frequency of anaphylaxis.

PMID:
42844895
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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