Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab.

Area of Science:

• Immunology
• Allergy and Immunology
• Clinical Trials

Background:

• Multifood oral immunotherapy (mOIT) combined with anti-IgE (omalizumab) offers rapid and effective multi-food desensitization.
• The precise immune mechanisms driving omalizumab-facilitated mOIT desensitization require further elucidation.

Purpose of the Study:

• To comprehensively investigate the immune changes associated with omalizumab-assisted mOIT.
• To understand the cellular and molecular mechanisms underlying rapid food desensitization.

Main Methods:

• Phase 2 clinical trial (NCT02643862) involving mOIT and omalizumab treatment.
• Analysis of peripheral blood mononuclear cells (PBMCs) and plasma using mass cytometry, component-resolved diagnostics, basophil activation tests, and Luminex.
• Immune profiling at baseline, week 8 (omalizumab-only), and week 36 (post-mOIT).

Main Results:

• Omalizumab-alone phase showed decreased IL-4+ T cells, GPR15, and CXCR3 expression, alongside CCR4 and CLA upregulation on specific T-cell subsets.
• Antigen-presenting cells exhibited downregulated CD86 expression.
• Post-mOIT, reduced pro-inflammatory cytokines (IL-17) and an attenuated Th2 phenotype were observed, indicated by decreased IL-4+ T cells, increased IgG4/IgE ratio, and reduced basophil activation.

Conclusions:

• This study offers novel insights into the immune mechanisms of desensitization during omalizumab-facilitated mOIT.
• The findings support the induction of complex immune system changes by OIT, highlighting the role of T-cell modulation and reduced inflammation.