Severe Food Allergy Reactions Are Associated With α-Tryptase

To assess the associations between hereditary α-tryptasemia (HαT), tryptase genotype, and severity of food allergy reactions. The first paragraph of our “REVIEWER COMMENTS” gives the reader some background on tryptase genes.

There were 2 cohorts: (1) banked blood or saliva samples from patients previously enrolled in an NIAID study of the natural history of food allergy and (2) buccal swabs from peanut allergic (PNA) patients who reacted during open oral food challenges (OFC) at Lurie Children’s Hospital (Chicago).

Tryptase genotyping was performed on the samples from both cohorts. The primary outcome for the NIAID cohort was a history of ≥1 episode of food-induced anaphylaxis and the secondary outcome was the most severe reported anaphylactic reaction graded by the Severity Grading Scale for Acute Reactions (SGSAR). The primary outcome for the PNA cohort was severe versus mild reaction during OFC, whereas the secondary outcomes were SGSAR and a modified Bock/PRACTALL score.

There were 119 subjects (NIAID: n = 82, median age 9 years; PNA: n = 37, median age 9 years [ns]). There were no demographic or clinical differences between cohorts or between those with severe (n = 21) and mild (n = 16) OFC reaction in the PNA group. The PNA OFC SGSAR and Bock/PRACTALL scores were higher in those with severe versus mild reactions (P = .001) reactions. Of the 119 subjects, 7% had HαT and 26% had ββ/ββ genotype (as compared with the population prevalence of 32%). ββ/βα was the most common genotype (40%) among the subjects, as it is in the general population. In the NIAID cohort, all 3 patients with HαT had food-induced anaphylaxis. Individuals with any α-tryptase were significantly more likely to have a history of food induced anaphylaxis than those with only β-tryptase (ββ/ββ, P = .026) and higher SGSAR scores trending toward significance (P = .07). Of the PNA cohort, 2 of 21 (10%) subjects with severe reactions had HαT as compared with none with mild reactions. Only 1 of 6 (17%) PNA subjects with no α-tryptase (ββ/ββ) had a severe reaction, whereas 20 of 31 (65%) of those with any α-tryptase had severe reactions (P = .066). Those with α-tryptase had higher SGSAR scores than those with ββ/ββ genotypes (P = .003). Furthermore, there were significant correlations between α-tryptase gene copy number and higher SGSAR and Bock/PRACTALL scores (P = .008 and P = .003, respectively).

The presence of α-tryptase alleles at TPSAB1 is associated with more severe food-induced reactions, including increased risk of anaphylaxis. The tryptase genotype and in particular the α-tryptase allele copy number may be useful biomarkers and independent risk factors for severe food allergies.

The tryptase genes relevant to this study are TPSAB1, that can code for either α or β-tryptase, and TPSB2, that only codes for β-tryptase. Thus, there are only 4 normal tryptase genotypes ββ/ββ, ββ/βα, βα/βα, and ββ/αα. α-tryptase is constitutively expressed, whereas β-tryptase is stored in mast cell granules and expressed upon mast cell activation. HαT is present when there is gene duplication at TPSAB1 with more than 1 copy of the allele coding for α-tryptase on 1 chromosome and at least 1 on the other (eg, 3 or more total α-tryptase genes). In addition to the findings in this study, patients with HαT and either venom allergy, idiopathic anaphylaxis, or systemic mastocytosis have greater risk for severe anaphylaxis. In a large case series, 100% of HαT subjects had baseline serum tryptase levels > 8 ng/mL (normal <11.4 ng/mL). Therefore, it behooves us to be on the lookout for HαT. Subjects with idiopathic anaphylaxis, venom anaphylaxis, severe food reactions, and others should have a baseline serum tryptase measured. If it is >8 ng/mL, the TBSAB1 genotype should be evaluated (https://www.genebygene.com/service/tryptase). All patients with anaphylaxis should carry epinephrine autoinjectors.