Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics

Area of Science:

• Immunology
• Allergology
• Omics Sciences

Background:

• Sublingual allergen-specific immunotherapy (SLIT) controls grass pollen allergy but its systemic effects and kinetics remain poorly understood.
• The influence of patient sensitization phenotype (mono- vs. poly-sensitized) on SLIT outcomes requires further investigation.
• Omics sciences offer potential for novel insights into SLIT mechanisms.

Purpose of the Study:

• To investigate the systemic effects and kinetics of SLIT in grass pollen allergy.
• To explore the impact of patient sensitization phenotype on SLIT-induced changes.
• To utilize metabolomics and transcriptomics to understand SLIT's influence on immune responses.

Main Methods:

• A 2-year, double-blind, placebo-controlled trial involving 47 grass pollen-allergic patients using GRAZAX®.
• Immunological assays (sIgE, sIgG4, ISAC) and omics analyses (metabolomics, transcriptomics) on patient samples.
• Stratification of patients into mono- and poly-sensitized groups to compare treatment effects.

Main Results:

• Serological changes aligned with previous findings; minimal systemic inflammation changes observed after 2 years of SLIT.
• Poly-sensitized patients exhibited higher baseline inflammation compared to mono-sensitized patients.
• SLIT led to reduced mast cell and phagocyte activity in mono-sensitized patients, alongside effector cell desensitization.

Conclusions:

• Two years of SLIT demonstrated effector cell desensitization primarily in mono-sensitized patients.
• This desensitization may correlate with clinical improvement and explain the loss of effect upon SLIT discontinuation.
• Systemic effects of SLIT are subtle, with phenotype-specific immune modulations observed.