Redefining tryptase norms in the pediatric population reveals sex-based differences: Clinical implications

Abstract

The measurement of serum basal tryptase (sBT) levels is a widely used analysis for the diagnosis of mast cell (MC) activation disorders. Knowledge of an individual's sBT level can be used to diagnose hereditary alpha-tryptasemia (HαT), a genetic trait caused by a duplication/amplification of the alpha-1 allele of the TPSAB1 gene¹ which induces an elevation of sBT levels. The prevalence of HαT is around 5% in the general population¹ but is higher along people with clonal MC disorders.² HαT is associated with an elevated risk of hymenoptera venom, grade IV idiopathic anaphylaxis, particularly in the context of mastocytosis. Several studies have highlighted the relationship between sBT levels and the risk and severity of anaphylaxis in children with food allergy.^{3, 4} The sBT threshold for HαT is set at 8.0 ng/mL according to the 95th percentile, primarily based on adult populations, with limited data on children.^{5, 6} Both the influence of age on sBT levels and the threshold for an elevated sBT in pediatric patients are subject to debate. The study aimed to confirm the 8.0 ng/mL sBT threshold in the general pediatric population.

The study included 398 children, with a median (range) age of 8 years (0–17) and a male-to-female ratio of 1.37. The median [95% confidence interval (CI)] (range) sBT was 3.2 [3.0–3.4] (1.0–25.8) ng/mL. Eight patients (2.7%) had a sBT level >8.0 ng/mL. The median sBT levels were similar in all age groups except the youngest: the median value of 4.3 ng/mL in infants under 1 year old (y. o.) was significantly higher than the median value for all the other age groups pooled (3.0 ng/mL; p < 0.001, Figure 1). The median (range) value was significantly higher in males than in females (3.4 (1.0–25.8) ng/mL vs. 2.9 (1.0–12.0) ng/mL, respectively; p = 0.001). We next looked at sex differences in the sBT levels across age groups and found a significant sex difference only in the oldest age group (13–17 y. o.). The median [95% CI] (range) sBT level was 3.7 [3.2–4.6] (1.3–16.9) ng/mL for males and 2.2 [2.2–3.1] (1.0–8.5) ng/mL for females (p = 0.001) (Table 1). Unlike boys, for girls aged 5 and above, the 95th percentile curve for tryptase values remains below 7.0 ng/mL (Figure 2). Then we compared serum tryptase levels between adult males and females using a cohort of 2204 adults (M/F ratio:0.58) with a tryptase assay prescribed as part of their care. There was a significant sex difference in the median [95% CI] serum tryptase level in the 18–38 y. o. group (4.6 [6.3–11.4] ng/mL for males vs. 3.7 ng/mL [4.9–6.9] for females; p < 0.001) and in the 39–58 y. o. group (5.4 [7.3–18.5] ng/mg for males vs. 4.6 [6.6–8.6] ng/mL for females; p < 0.001). The sex difference in the older age group (>58 years) was not significant (Figure S1).

Our present results demonstrate that the sBT is significantly higher in infants <1 y. o. and are in line with previous reports.^{5, 6} Our findings align with literature showing lower sBT levels in females, potentially influenced by sex hormones puberty.⁶ We included adults, despite recruitment bias (samples from medical care), to study sex differences in sBT levels. Results showed lower sBT levels in females up to menopause, suggesting sex hormones impact sBT. This effect and the associated mechanisms remain understudied. The present study provided robust and new data on sBT levels in the general pediatric population and highlights that the “adult” threshold of 8.0 ng/mL could also be used to screen boys for HαT. However, for girls from age 5, a 7.0 ng/mL threshold might be more appropriate. We provide physicians with an online sBT 95th percentile calculator by age and sex: https://tools.institutimagine.org/pediatryptasecalc/. Further studies on the predictive qualities of sBT levels for HαT, considering sex differences, are needed to confirm sBT threshold values.

This research did not receive any specific funding from agencies or organizations in the public, commercial or not-for-profit sectors. L.P. was funded by the Bettencourt Schueller Foundation.

The authors declare no conflicts of interest with regard to the present study.