Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma
Abstract Background Both 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-03-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.282 |
| _version_ | 1818922882215968768 |
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| author | Stephany Sánchez‐Ovando Katherine J. Baines Daniel Barker Peter A. Wark Jodie L. Simpson |
| author_facet | Stephany Sánchez‐Ovando Katherine J. Baines Daniel Barker Peter A. Wark Jodie L. Simpson |
| author_sort | Stephany Sánchez‐Ovando |
| collection | DOAJ |
| description | Abstract Background Both 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. Methods This 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. Results Gene 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 Relevance There 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. |
| first_indexed | 2024-12-20T02:00:36Z |
| format | Article |
| id | doaj.art-b804bfc6ab2f488e9143b8639b4c26ce |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-12-20T02:00:36Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-b804bfc6ab2f488e9143b8639b4c26ce2022-12-21T19:57:21ZengWileyImmunity, Inflammation and Disease2050-45272020-03-0181404910.1002/iid3.282Six gene and TH2 signature expression in endobronchial biopsies of participants with asthmaStephany Sánchez‐Ovando0Katherine J. Baines1Daniel Barker2Peter A. Wark3Jodie L. Simpson4Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs University of Newcastle New South Wales AustraliaFaculty of Health and Medicine, Priority Research Centre for Healthy Lungs University of Newcastle New South Wales AustraliaFaculty of Health and Medicine University of Newcastle New South Wales AustraliaFaculty of Health and Medicine, Priority Research Centre for Healthy Lungs University of Newcastle New South Wales AustraliaFaculty of Health and Medicine, Priority Research Centre for Healthy Lungs University of Newcastle New South Wales AustraliaAbstract Background Both 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. Methods This 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. Results Gene 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 Relevance There 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.https://doi.org/10.1002/iid3.282asthmaendobronchial biopsyinflammationinflammatory phenotypes |
| spellingShingle | Stephany Sánchez‐Ovando Katherine J. Baines Daniel Barker Peter A. Wark Jodie L. Simpson Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma Immunity, Inflammation and Disease asthma endobronchial biopsy inflammation inflammatory phenotypes |
| title | Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma |
| title_full | Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma |
| title_fullStr | Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma |
| title_full_unstemmed | Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma |
| title_short | Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma |
| title_sort | six gene and th2 signature expression in endobronchial biopsies of participants with asthma |
| topic | asthma endobronchial biopsy inflammation inflammatory phenotypes |
| url | https://doi.org/10.1002/iid3.282 |
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