Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy
© 2024 Regeneron Pharmaceuticals Inc and The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:79 |
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| Enthalten in: |
Allergy - 79(2024), 4 vom: 18. Apr., Seite 894-907 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wipperman, Matthew F [VerfasserIn] |
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| Links: |
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| Themen: |
420K487FSG |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/all.16001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367703289 |
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| 245 | 1 | 0 | |a Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy |
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| 500 | |a Date Revised 01.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Regeneron Pharmaceuticals Inc and The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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