Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma.

Stephany Sánchez‐Ovando,Katherine J Baines,Jodie L Simpson,Peter A Wark,Daniel Barker

doi:10.1002/iid3.282

Stephany Sánchez‐Ovando, Katherine J Baines + Show 3 more

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https://doi.org/10.1002/iid3.282

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Abstract

BackgroundBoth the six gene signature (6GS: CPA3, DNASE1L3, CLC, IL1B, ALPL, and CXCR2) and T‐helper 2 signature (TH2S: CLCA1, SERPINB2, and POSTN) are proposed as biomarkers in the identification of inflammatory phenotypes of asthma in induced sputum and epithelial brushings, respectively. The aim of this study was to explore patterns of gene expression of known signatures, 6GS and TH2S in endobronchial biopsies.MethodsThis was an exploratory cross‐sectional study of gene expression in endobronchial biopsies of 55 adults with asthma and 9 healthy controls (HC). The expression of the 6GS and TH2S was determined by quantitative polymerase chain reaction. Correlations with clinical and cellular characteristics were performed, and receiver operating characteristic was utilized to assess signatures' ability to predict asthma from HC and inflammatory phenotypes.ResultsGene expression of DNASE1L3 (P = .045) was upregulated in asthma compared with HC, and IL1B (P = .017) was upregulated in neutrophilic asthma compared with non‐neutrophilic asthma. In asthma, the expression of CPA3 was negatively associated with ICS daily dose (r = −.339; P = .011), IL1B expression was positively associated with bronchial lavage fluid (BLF) total cell count (r = .340; P = .013) and both CLC and POSTN expression were associated with lymphocytes percentage in BLF (r = −.355, P = .009; r = −.300, P = .025, respectively). Both 6GS (area under curve [AUC] = 86.3%; P = .017) and TH2S (AUC = 72.7%; P = .037) could significantly predict asthma from HC. In addition, 6GS can identify neutrophilic (AUC = 93.2%; P = .005) and TH2S identifies eosinophilic (AUC = 62.7%; P = .033) asthma.Conclusions and Clinical RelevanceThere was increased expression of DNASE1L3 in asthma and IL1B in neutrophilic asthma. These results show similar upregulated patterns of expression in two genes of the 6GS in endobronchial biopsies, previously identified in sputum. The upregulation of DNASE1L3 and IL1B suggests that common mechanisms may be at play throughout the airway.

Highlights

Asthma is a heterogeneous disease with multiple clinical and inflammatory manifestations.[1]
This study explored the expression of the gene signatures 6GS and T‐helper 2 signature (TH2S) previously reported in sputum and epithelial brushings in endobronchial.[2,13]
We observed upregulation of two genes of the 6GS, an upregulation of DNASE1L3 in asthma compared with healthy controls (HC), and upregulation of IL1B in neutrophilic asthma compared with non‐ neutrophilic asthma

Summary

Introduction

Asthma is a heterogeneous disease with multiple clinical and inflammatory manifestations.[1]. Corticosteroids have a pronounced effect in most patients, 30% to 40% of patients have a poor response to traditional treatment approaches and high sputum neutrophil counts have been linked to reduced responsiveness to corticosteroids as well as more severe asthma.[11,12] The identification of phenotypes of asthma based on the mechanisms of the disease pathogenesis that reflect clinical features offers the promise to better predict clinical outcomes and personalize response to treatment Such an approach has utilized the identification of gene biomarker signatures that reflects pathogenic mechanisms associated with different airway inflammatory phenotypes of asthma. The upregulation of DNASE1L3 and IL1B suggests that common mechanisms may be at play throughout the airway

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