Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy.
Allergy
; 79(4): 894-907, 2024 04.
Article
em En
| MEDLINE
| ID: mdl-38279910
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Monoclonais Humanizados
/
Transcriptoma
/
Rinite Alérgica
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
Allergy
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos