Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr;79(4):894-907.
doi: 10.1111/all.16001. Epub 2024 Jan 27.

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

Matthew F Wipperman  1 , Kaitlyn M Gayvert  1 , Amanda Atanasio  1 , Claire Q Wang  1 , Jonathan Corren  2 , Angelica Covarrubias  3 , Ian Setliff  1 , Erica Chio  1 , Elizabeth Laws  4 , Kelley Wolfe  4 , Sivan Harel  1 , Jennifer Maloney  1 , Gary Herman  1 , Jamie M Orengo  1 , Wei Keat Lim  1 , Sara C Hamon  1 , Jennifer D Hamilton  1 , Meagan P O'Brien  1
Affiliations

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

Matthew F Wipperman et al. Allergy. 2024 Apr.

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.

Trial registration: ClinicalTrials.gov NCT03558997.

Keywords: RNA; SCIT; allergic rhinitis; dupilumab; gene expression; transcriptomics.

PubMed Disclaimer

References

REFERENCES

    1. Bousquet J, Anto JM, Bachert C, et al. Allergic rhinitis. Nat Rev Dis Primers. 2020;6(1):95.
    1. Gandhi NA, Bennett BL, Graham NM, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35‐50.
    1. Leaker BR, Malkov VA, Mogg R, et al. The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL‐5 and IL‐13), the inflammasome (IL‐1β), and complement. Mucosal Immunol. 2017;10(2):408‐420.
    1. Fallon PG, Jolin HE, Smith P, et al. IL‐4 induces characteristic Th2 responses even in the combined absence of IL‐5, IL‐9, and IL‐13. Immunity. 2002;17(1):7‐17.
    1. Le Floch A, Allinne J, Nagashima K, et al. Dual blockade of IL‐4 and IL‐13 with dupilumab, an IL‐4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020;75(5):1188‐1204.

Publication types

Associated data

LinkOut - more resources