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

V. Dwivedi, K. Schmidthaler, H. Demir, et al. Allergy (2026): 1–12, https://doi.org/10.1111/all.70387. 

ABSTRACT

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

Graphical Abstract: HDM-pSLIT induced IgG, IgG1, and IgG4 specific
to major HDM allergens in sensitized non-allergic preschool children
without increasing HDM-sIgE. It blunted the development of new
sensitizations and reduced HDM reactivity in skin and basophils.
HDM-pSLIT treated children displayed a blocking effect on
HDM-induced basophil activation.
HDM, house dust mite; Ig, immunoglobulin; pSLIT,
preventively administered sublingual immunotherapy.

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

Eighteen children received HDM-SLIT (mean age = 4.26 ± 0.37 years, eight females) and 15 placebo (mean age = 4.16 ± 0.59 years, nine females). HDM-SLIT increased Der p 1-sIgG levels between baseline and EOT versus placebo (effect size = 3.11 [95% CL 1.36–4.82], p = 0.001). Additional changes induced by HDM-SLIT were: increased levels of HDM-sIgG1 and -sIgG4, 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.

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