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Proteomic signatures of eosinophilic and neutrophilic asthma from serum and sputumResearch in context

التفاصيل البيبلوغرافية
العنوان: Proteomic signatures of eosinophilic and neutrophilic asthma from serum and sputumResearch in context
المؤلفون: Khezia Asamoah, Kian Fan Chung, Nazanin Zounemat Kermani, Barbara Bodinier, Sven-Erik Dahlen, Ratko Djukanovic, Pankaj K. Bhavsar, Ian M. Adcock, Dragana Vuckovic, Marc Chadeau-Hyam
المصدر: EBioMedicine, Vol 99, Iss , Pp 104936- (2024)
بيانات النشر: Elsevier, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Proteomics, LASSO, Sputum, Serum, Eosinophil, Neutrophil, Medicine, Medicine (General), R5-920
الوصف: Summary: Background: Eosinophilic and neutrophilic asthma defined by high levels of blood and sputum eosinophils and neutrophils exemplifies the inflammatory heterogeneity of asthma, particularly severe asthma. We analysed the serum and sputum proteome to identify biomarkers jointly associated with these different phenotypes. Methods: Proteomic profiles (N = 1129 proteins) were assayed in sputum (n = 182) and serum (n = 574) from two cohorts (U-BIOPRED and ADEPT) of mild-moderate and severe asthma by SOMAscan. Using least absolute shrinkage and selection operator (LASSO)-penalised logistic regression in a stability selection framework, we sought sparse sets of proteins associated with either eosinophilic or neutrophilic asthma with and without adjustment for established clinical factors including oral corticosteroid use and forced expiratory volume. Findings: We identified 13 serum proteins associated with eosinophilic asthma, including 7 (PAPP-A, TARC/CCL17, ALT/GPT, IgE, CCL28, CO8A1, and IL5-Rα) that were stably selected while adjusting for clinical factors yielding an AUC of 0.84 (95% CI: 0.83–0.84) compared to 0.62 (95% CI: 0.61–0.63) for clinical factors only. Sputum protein analysis selected only PAPP-A (AUC = 0.81 [95% CI: 0.80–0.81]). 12 serum proteins were associated with neutrophilic asthma, of which 5 (MMP-9, EDAR, GIIE/PLA2G2E, IL-1-R4/IL1RL1, and Elafin) complemented clinical factors increasing the AUC from 0.63 (95% CI: 0.58–0.67) for the model with clinical factors only to 0.89 (95% CI: 0.89–0.90). Our model did not select any sputum proteins associated with neutrophilic status. Interpretation: Targeted serum proteomic profiles are a non-invasive and scalable approach for subtyping of neutrophilic and eosinophilic asthma and for future functional understanding of these phenotypes. Funding: U-BIOPRED has received funding from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115010, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007–2013), and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in-kind contributions (www.imi.europa.eu). ADEPT was funded by Johnson & Johnson/Janssen pharmaceutical Company.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396423005029; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2023.104936
URL الوصول: https://doaj.org/article/9d60fe4ea80c4d5ebe54f572eafa9d2e
رقم الأكسشن: edsdoj.9d60fe4ea80c4d5ebe54f572eafa9d2e
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2023.104936