Preventive Application of House Dust Mite‐Sublingual Immunotherapy Induces Blocking Antibodies in Sensitized Preschool Children

BACKGROUND: Sublingual allergen immunotherapy (SLIT) is an effective treatment for immunoglobulin (Ig)E-mediated allergies. Its success is associated with allergen-specific (s)IgG, which blocks IgE-mediated mechanisms. Preventive effects of SLIT in children before allergy-symptom onset remain largely unexplored. METHODS: A randomized trial was conducted between October 06, 2017 and December 15, 2022, which included house dust mite (HDM)-sensitized preschool children (aged 3-5 years) showing no allergy symptoms. They were randomized (2:2 blocks) to HDM-SLIT (300 index of reactivity/day, Staloral) or placebo solution for 2 years. Children receiving > 4 months of treatment were included in the analysis. Primary objective of the study was to compare the groups for change in major HDM allergen-Der p 1-sIgG levels from baseline to end of treatment (EOT). Secondary objectives were to compare longitudinal changes (at 4 and 12 months, and EOT) in the (i) levels of HDM-sIgG subclasses and -sIgE using ImmunoCAP/-ISAC and/or ELISA (ii) Der p-reactivity in skin and basophils using skin prick test and basophil activation test (BAT), (iii) sensitization status defined as sIgE-positivity in skin and/or serum, and (iv) Der p-sIgE-blocking activity using inhibition-BAT. RESULTS: , no long-term increase in HDM-sIgE levels, reduced Der p-reactivity in skin and basophils (p values ≤ 0.05), and blunted development of new sensitizations. Sera from HDM-SLIT treated individuals displayed blocking activity on basophils (p values ≤ 0.05). CONCLUSIONS: Preventive application of HDM-SLIT in allergy-prone children induces immunomodulatory effects early during treatment (elevated sIgG levels with blocking activity and reduced effector cell responses), thereby revealing potential to interfere with allergy development. TRIAL REGISTRATION: EudraCT#2016-002844-18.