Severe food allergy reactions are associated with α-tryptase

Abstract

Background: Increased TPSAB1 copy numbers encoding ⍺-tryptase are associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis.

Objective: The primary objective was to assess the association between ⍺-tryptase and severity of food allergy.

Methods: A total of 119 subjects underwent tryptase genotyping; 82 of them were from an observational food allergy cohort at the National Institute of Allergy and Infectious Disease (NIAID), and 37 were from a cohort of children who reacted to peanut oral food challenge (OFC) at Lurie Children's Hospital of Chicago. The primary predictor was presence or absence of ⍺-tryptase. The primary outcomes for both cohorts were measures of severity of food allergy reaction. Secondary outcomes included OFC symptom scores (Bock/Practical Allergy [PRACTALL] and Severity Grading Score for Acute Reactions [SGSAR]). Correlation between total α-tryptase isoforms and OFC scores was also assessed to account for gene dosage effects.

Results: Among the subjects in the NIAID cohort, the presence of ⍺-tryptase was associated with a higher prevalence of food-triggered anaphylaxis than in those with only β-tryptase (P = .026). Similarly, only 1 of 6 subjects in the OFC cohort with only β-tryptase (17%) had a severe reaction, whereas 20 of 31 of subjects with α-tryptase (65%) had a severe reaction (P = .066). Subjects with ⍺-tryptase also had higher total SGSAR scores than did the subjects with no ⍺-tryptase (P = .003). In addition, there were also significant positive correlations between ⍺-tryptase isoform copy numbers and both higher total SGSAR and Bock/PRACTALL OFC scores (P = .008 and P = .003, respectively).

Conclusion: The presence of α-tryptase in subjects is correlated with a higher prevalence of anaphylaxis or severe reaction to food than in subjects without any α-tryptase.

Keywords: Food allergy; anaphylaxis; hereditary α-tryptasemia; peanut allergy; α-tryptase.

Figure 1.

Increased α-tryptase is associated with increased prevalence and severity of anaphylaxis to food in subjects with known food allergy. A. Prevalence of anaphylaxis triggered by food reported by in patients with history of food allergy by relative α-tryptase encoding copy number in the NIAID observational cohort. Numbers above each bar represent the number of subjects (total n=82) in each group by tryptase genotype [(either 0, 1, 2, or >2 α-tryptase copies/HαT (≥1 α-tryptase replication)]. Analysis performed using Fisher’s exact test. B. Most severe reported anaphylactic reaction Severity Grading Scale for Acute Reactions (SGSAR) score by relative α-tryptase encoding copy number. Wilcoxon tests assessed for association between presence of any α-tryptase and SGSAR score; Spearman’s rank correlation was also performed between total number of α-tryptase isoforms and SGSAR to assess for possible gene dosage effects.

Figure 2.

Increased α-tryptase isoform expression is associated with increased severity of reaction to peanut oral food challenge (OFC). A. Subjects with any α-tryptase isoforms were more likely to have higher Severity Grading Score for Acute Reactions (SGSAR) scores as compared to subjects with no α-tryptase isoforms. B. There was a statistically significant positive correlation between α-tryptase isoform copy numbers and total modified Bock/PRACTALL symptom score. Wilcoxon tests assessed for association between presence of any α-tryptase and OFC scores; Spearman’s rank correlation was also performed between total number of α-tryptase isoforms and SGSAR to assess for possible gene dosage effects.