Journal article
Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma
- Abstract:
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Background
Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations.Objective
Our study aimed to explore the corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway.Method
The MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for SEA. We analysed paired sputum (n=16) and plasma (n=25) samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed additional sputum proteins using ELISA.Results
In patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated.
Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated.Conclusion
At stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Supplementary materials, pdf, 2.6MB, Terms of use)
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(Preview, Version of record, pdf, 3.5MB, Terms of use)
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- Publisher copy:
- 10.1016/j.jaci.2024.07.020
Authors
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 211050/Z/18/Z
- Publisher:
- Elsevier
- Journal:
- Journal of Allergy and Clinical Immunology More from this journal
- Volume:
- 154
- Issue:
- 5
- Pages:
- 1146-1158
- Publication date:
- 2024-08-01
- Acceptance date:
- 2024-07-15
- DOI:
- EISSN:
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1097-6825
- ISSN:
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0091-6749
- Language:
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English
- Keywords:
- Pubs id:
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2016153
- Local pid:
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pubs:2016153
- Deposit date:
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2024-07-17
- ARK identifier:
Terms of use
- Copyright holder:
- Howell et al.
- Copyright date:
- 2024
- Rights statement:
- © 2024 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Notes:
- This research was funded in whole or in part by the Welcome Trust (211050/Z/18/Z). For the purposes of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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