Sputum mast cell/basophil gene expression relates to inflammatory and clinical features of severe asthma - 04/08/21
Abstract |
Background |
Mast cells (MCs) and basophils are important in asthma pathophysiology, however direct measurement is difficult, and clinical and inflammatory associations in severe asthma are poorly understood. Transcriptomic hallmarks of MCs/basophils may allow their measurement in sputum using gene expression.
Objectives |
This study sought to develop and validate a sputum MC/basophil gene signature and investigate its relationship to inflammatory and clinical characteristics of severe asthma.
Methods |
A total of 134 candidate MC/basophil genes (identified by the Immunological Genome Project Consortium) were screened in sputum microarray for differential expression among control subjects (n = 18), patients with eosinophilic (n = 29), and patients with noneosinophilic asthma (n = 30). Candidate genes were validated by confirming correlation of gene expression with flow cytometry-quantified sputum MCs and basophils in a separate asthma cohort (n = 20). The validated gene signature was measured in a severe asthma cohort (n = 81), and inflammatory and clinical associations were tested.
Results |
Through microarray screening and subsequent validation, we found quantitative PCR gene expression of 8 targets correlated with sputum MCs/basophils: TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2. In severe asthma, MC/basophil genes were associated with eosinophilic airway inflammation (GATA2, TPSB2, CPA3, GPR56, HDC, SOCS2), blood eosinophils (TPSB2, CPA3, GATA2, SOCS2, FCER1A, HDC), fractional exhaled NO (GATA2, SOCS2), decreased lung function (KIT, ENO2), and moderate exacerbation history (GATA2, SOCS2).
Conclusions |
Quantitative PCR–based measures reflect varying sputum MC/basophil abundance, demonstrating associations of MCs/basophils with eosinophilic inflammation, spirometry and exacerbation history in severe asthma.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Mast cells, basophils, asthma, gene expression, inflammation
Abbreviations used : ACQ, AHR, ASM, AUROC, BR, EA, Feno, FVC, LASSO, MC, NA, NEA, NNA, PBEs, ppb
Plan
| This work was supported by grants from the National Health and Medical Research Council (G1400017); University of Newcastle (G1101050); Hunter Medical Research Institute (G1101169); and John Hunter Hospital Charitable Trust (G1200211). M.F. received funding from a Thoracic Society of Australia and New Zealand/AstraZeneca Respiratory Research Fellowship. K.J.B. was supported by a Lung Foundation Australia chronic obstructive pulmonary disease research fellowship. Sponsors had no role in study design, analysis or interpretation of results, or preparation of manuscript. |
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| Disclosure of potential conflict of interest: P.G. Gibson has received personal fees from AstraZeneca, GlaxoSmithKline and Novartis; and grants from AstraZeneca and GlaxoSmithKline outside the submitted work. V.M. McDonald has received research funding from the National Health and Medical Research Council, the Ramaciotti Foundation, the University of Newcastle, The Hunter Medical Research Institute, and the John Hunter Hospital Research Grants Scheme in relation to the presented work; personal fees from AstraZeneca, GlaxoSmithKline, and Menarini; and grants from AstraZeneca and GlaxoSmithKline outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 148 - N° 2
P. 428-438 - août 2021 Retour au numéro
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