Higher levels of basal serum tryptase are associated with sensitization, FeNO, allergic morbidity, and lower control of allergic asthma in teenagers from the PARIS birth cohort
Authors: Yannick Chantran, Simone Choi, Céline Roda, Pascale Nicaise‐Roland, Luc de Chaisemartin, Sylvie Chollet‐Martin, Michel Arock, Fanny Rancière, Isabelle Momas
Journal: Allergy (2024)

Basal serum tryptase (bST) is a critical biomarker to confirm acute tryptase elevation in suspected mast cell activation like anaphylaxis and to evaluate mast cell burden in systemic mastocytosis workup. Better appraisal of genetic, physiological, environmental, and pathological factors influencing bST levels could bring significant improvement in bST interpretation.1 Regarding allergic conditions, hymenoptera venom anaphylaxis aside, previous reports pinpointed bST elevation in atopic dermatitis,2 or severe asthma.3 To date, no population-based cohort focused on the associated between bST levels and allergy before adulthood. This cross-sectional study aimed to assess the association between bST levels and allergy-related outcomes among teenagers participating to the PARIS study (Pollution and Asthma Risk: an Infant Study), a French ongoing population-based prospective birth cohort. Our population study included 610 teenagers who received self-administered questionnaires, blood sampling and other medical investigations during a health check-up at age 15/16 years. Sensitization to a source was considered in case of positive Skin Prick tests and/or specific IgE ≥0.35 kUA/L. The fraction of exhaled nitric oxide (FeNO) was measured. Current asthma, rhinitis and dermatitis were defined according to clinical criteria of the MeDALL consortium. Food and drug reactions were defined based on doctor-diagnosed allergy. Asthma control was evaluated by the Asthma Control Test (ACT). Circulating bST concentrations were evaluated using the ImmunoCAP™ Tryptase kit (ThermoFisher Scientific). More detailed information on methods is available in the online repository. Baseline sociodemographic characteristics in our study population are presented in Table S1, and allergy-related health outcomes in Table S2. The distribution of bST values followed a bimodal distribution with one mode around the median (4.2 μg/L), and another around 10 μg/L (Figure S1). This second group accounted for 4%–5% participants. Of note, the overall and intragroup bST distribution deviated from the normal even after log- and square root-transformations, and bST tertiles were used in following analyses. The 95th bST percentile was 7.7 μg/L (Table S3). After adjustment, bST levels were positively associated with male sex (aOR = 1.37, 95% CI: 1.006, 1.87), the absence of history of active tobacco use (aOR = 1.59, 95% CI: 1.12, 2.26), age (aOR = 1.71, 95% CI: 1.05, 2.80, per +1 year), and body weight (aOR = 1.02, 95% CI: 1.002, 1.033, per +1 kg). Higher bST was associated with higher frequency of overall sensitization (p =.031), sensitization to inhaled allergens (p =.031) such as cat dander, grass or mugwort pollens, and sensitization to food allergens (p =.010) such as sesame (Table S1). Higher risk of sensitization to inhaled and food allergens for participants from the highest bST tertile were confirmed after adjustment for confounders (Figure 1). In addition, bST levels were positively associated with intermediate-to-high FeNO (≥ 25 ppb; p =.011; Table S2). This was confirmed after adjustment for potential confounders, including blood eosinophils and sensitization status, between the 3rd and the 1st bST tertiles (aOR = 2.07, 95% CI: 1.03, 4.23; Figure 1). Regarding hypersensitivity manifestations, higher bST levels were positively associated with drug reactions (p =.03, Table S2). In addition, adjustment for confounders revealed a positive association between bST levels and the risk of presenting hypersensitivity (aOR = 1.74, 95% CI: 1.09, 2.82), and sensitization-associated asthma (aOR = 2.48, 95% CI: 1.10, 5.99, Figure 1). Furthermore, asthmatic teenagers with high bST levels were more likely to present lower asthma control score (p =.042), especially in participants with IgE-mediated asthma (p =.033), but not with asthma in the absence of observed sensitization (p =.73) (Figure 2). In conclusion, in teenagers from a population-based birth cohort, we demonstrate that bST levels are positively associated with sensitization, FeNO levels, clinical manifestations including drug reactions and IgE-associated asthma, and lower ACT score. This is the first population-based study regarding bST levels and allergy before adulthood.4, 5 Considering bST levels are stable for years in a given individual,6 our results drive the hypothesis of bST as a potential tool to predict and stratify allergic phenotypes during early life (see Data S1 for additional discussion). Study conception and design: YC, IM. Data acquisition: YC, SC, CR, PNR, LdC, SCM, FR. Data analysis: YC, CR, FR, IM. Manuscript drafting: YC, SC, CR, FR, IM. Manuscript revision: YC, SC, CR, FR, MA, IM. We thank Sibylle Bachelier, Brigitte Berthier, Thierry Bokobza and Floriane Giraudon for their help in assessing tryptase levels. We thank Colette Mavier, Niclas Rydell, Heili Eriksson and Michael Spangfort for their support and fruitful discussion. We thank the Franch Society of Allergology for their support in studying tryptase and tryptase genotypes in the PARIS cohort. The PARIS cohort received fundings from: Paris Municipal Department of Social Action, Childhood, and Health (DASES); Université Paris Descartes; European collaborative program MeDALL, Grant/Award Number: FP7-261357. ThermoFisher Scientific Corporation provided reagents to assess circulating tryptase for this study. Y. Chantran serves in scientific advisory board for ThermoFisher Scientific, received honoraria from ThermoFisher Scientific, and research grants from Blueprint Medicines and ThermoFisher Scientific. M. Arock receives research grant from Blueprint Medicines, and serves on advisory boeard and receives honoraria from AB Science, Blueprint Medicines, Novartis and ThermoFisher Scientific. The rest of the authors declare that they have no relevant conflict of interest. Research data are not shared. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.