The following is a summary of “Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy,” published in the January 2024 issue of Allergy & Immunology by Wipperman, et al.

Nasal epithelial cells are pivotal in upholding barrier function and orchestrating immune signaling. However, in allergic rhinitis (AR), these functions can be disrupted due to inflammatory mediators. For a study, researchers sought to delve deeper into the mechanisms underpinning AR by scrutinizing transcriptome data from nasal brushing samples obtained from individuals both with and without AR.

Data were gleaned from a feasibility study encompassing individuals with and without AR to Timothy grass, alongside a clinical trial assessing the effects of 16 weeks of treatment with various interventions: dupilumab, a monoclonal antibody targeting interleukin (IL)-4Rα to curb type 2 inflammation; subcutaneous immunotherapy with Timothy grass (SCIT), which modulates allergic responses through diverse mechanisms; SCIT combined with dupilumab; or placebo. Using nasal brushing samples from these studies, distinct gene signatures were delineated for AR disease and post-nasal allergen challenge (NAC), and the influence of study drugs on these signatures was examined.

Treatment with dupilumab (NES = -1.73, P = .002) or SCIT + dupilumab (NES = -2.55, P < .001), but not SCIT alone (NES = +1.16, P = .107), significantly suppressed the AR disease signature. Similarly, dupilumab (NES = -2.55, P < .001), SCIT (NES = -2.99, P < .001), and SCIT + dupilumab (NES = -3.15, P < .001) all mitigated the NAC gene signature.

The findings underscored the significant contribution of type 2 inflammation to the pathophysiology of AR. They suggested that inhibiting the type 2 pathway with dupilumab may normalize gene expression in nasal tissue affected by AR.

Reference: onlinelibrary.wiley.com/doi/10.1111/all.16001