Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy

Matthew F. Wipperman, Kaitlyn M. Gayvert, Amanda Atanasio, Claire Q. Wang, Jonathan Corren, Angelica Covarrubias, Ian Setliff, Erica Chio, Elizabeth Laws, Kelley Wolfe, Sivan Harel, Jennifer Maloney, Gary Herman, Jamie M. Orengo, Wei Keat Lim, Sara C. Hamon, Jennifer D. Hamilton, Meagan P. O'Brien

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Nasal epithelial cells are important regulators of barrier function and immune signaling; however, in allergic rhinitis (AR) these functions can be disrupted by inflammatory mediators. We aimed to better discern AR disease mechanisms using transcriptome data from nasal brushing samples from individuals with and without AR. Methods: Data were drawn from a feasibility study of individuals with and without AR to Timothy grass and from a clinical trial evaluating 16 weeks of treatment with the following: dupilumab, a monoclonal antibody that binds interleukin (IL)-4Rα and inhibits type 2 inflammation by blocking signaling of both IL-4/IL-13; subcutaneous immunotherapy with Timothy grass (SCIT), which inhibits allergic responses through pleiotropic effects; SCIT + dupilumab; or placebo. Using nasal brushing samples from these studies, we defined distinct gene signatures in nasal tissue of AR disease and after nasal allergen challenge (NAC) and assessed how these signatures were modulated by study drug(s). Results: Treatment with dupilumab (normalized enrichment score [NES] = −1.73, p =.002) or SCIT + dupilumab (NES = −2.55, p <.001), but not SCIT alone (NES = +1.16, p =.107), significantly repressed the AR disease signature. Dupilumab (NES = −2.55, p <.001), SCIT (NES = −2.99, p <.001), and SCIT + dupilumab (NES = −3.15, p <.001) all repressed the NAC gene signature. Conclusion: These results demonstrate type 2 inflammation is an important contributor to the pathophysiology of AR disease and that inhibition of the type 2 pathway with dupilumab may normalize nasal tissue gene expression.

Original languageEnglish
Pages (from-to)894-907
Number of pages14
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume79
Issue number4
DOIs
StatePublished - Apr 2024
Externally publishedYes

Keywords

  • RNA
  • SCIT
  • allergic rhinitis
  • dupilumab
  • gene expression
  • transcriptomics

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