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

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Multifood oral immunotherapy (mOIT) with omalizumab rapidly desensitizes patients to multiple foods. This study reveals key immune changes, including T-cell alterations and reduced inflammation, underlying this effective treatment.

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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.