Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma
Background: Amphiregulin (AREG) expression in asthmatic airways and sputum was shown to increase and correlate with asthma. However, no studies were carried out to evaluate the AREG level in blood and saliva of asthmatic patients.Objective: To measure circulating AREG mRNA and protein concentrations...
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Frontiers Media S.A.
2020-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2020.561866/full |
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DOAJ |
language |
English |
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Article |
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DOAJ |
author |
Mahmood Yaseen Hachim Mahmood Yaseen Hachim Noha Mousaad Elemam Rakhee K. Ramakrishnan Laila Salameh Ronald Olivenstein Ibrahim Yaseen Hachim Ibrahim Yaseen Hachim Thenmozhi Venkatachalam Bassam Mahboub Bassam Mahboub Saba Al Heialy Saba Al Heialy Rabih Halwani Rabih Halwani Qutayba Hamid Qutayba Hamid Qutayba Hamid Rifat Hamoudi Rifat Hamoudi Rifat Hamoudi |
spellingShingle |
Mahmood Yaseen Hachim Mahmood Yaseen Hachim Noha Mousaad Elemam Rakhee K. Ramakrishnan Laila Salameh Ronald Olivenstein Ibrahim Yaseen Hachim Ibrahim Yaseen Hachim Thenmozhi Venkatachalam Bassam Mahboub Bassam Mahboub Saba Al Heialy Saba Al Heialy Rabih Halwani Rabih Halwani Qutayba Hamid Qutayba Hamid Qutayba Hamid Rifat Hamoudi Rifat Hamoudi Rifat Hamoudi Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma Frontiers in Medicine asthma biomarkers saliva amphiregulin (AREG) non-invasive |
author_facet |
Mahmood Yaseen Hachim Mahmood Yaseen Hachim Noha Mousaad Elemam Rakhee K. Ramakrishnan Laila Salameh Ronald Olivenstein Ibrahim Yaseen Hachim Ibrahim Yaseen Hachim Thenmozhi Venkatachalam Bassam Mahboub Bassam Mahboub Saba Al Heialy Saba Al Heialy Rabih Halwani Rabih Halwani Qutayba Hamid Qutayba Hamid Qutayba Hamid Rifat Hamoudi Rifat Hamoudi Rifat Hamoudi |
author_sort |
Mahmood Yaseen Hachim |
title |
Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma |
title_short |
Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma |
title_full |
Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma |
title_fullStr |
Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma |
title_full_unstemmed |
Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma |
title_sort |
blood and salivary amphiregulin levels as biomarkers for asthma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2020-10-01 |
description |
Background: Amphiregulin (AREG) expression in asthmatic airways and sputum was shown to increase and correlate with asthma. However, no studies were carried out to evaluate the AREG level in blood and saliva of asthmatic patients.Objective: To measure circulating AREG mRNA and protein concentrations in blood, saliva, and bronchial biopsies samples from asthmatic patients.Methods: Plasma and Saliva AREG protein concentrations were measured using ELISA while PBMCs, and Saliva mRNA expression was measured by RT qPCR in non-severe, and severe asthmatic patients compared to healthy controls. Primary asthmatic bronchial epithelial cells and fibroblasts were assessed for AREG mRNA expression and released soluble AREG in their conditioned media. Tissue expression of AREG was evaluated using immunohistochemistry of bronchial biopsies from asthmatic patients and healthy controls. Publicly available transcriptomic databases were explored for the global transcriptomic profile of bronchial epithelium, and PBMCs were explored for AREG expression in asthmatic vs. healthy controls.Results: Asthmatic patients had higher AREG protein levels in blood and saliva compared to control subjects. Higher mRNA expression in saliva and primary bronchial epithelial cells plus higher AREG immunoreactivity in bronchial biopsies were also observed. Both blood and saliva AREG levels showed positive correlations with allergic rhinitis status, atopy status, eczema status, plasma periostin, neutrophilia, Montelukast sodium use, ACT score, FEV1, and FEV1/FVC. In silico analysis showed that severe asthmatic bronchial epithelium with high AREG gene expression is associated with higher neutrophils infiltration.Conclusion: AREG levels measured in a minimally invasive blood sample and a non-invasive saliva sample are higher in non-allergic severe asthma.Clinical ImplicationsThis is the first report to show the higher level of AREG levels in blood and saliva of non-allergic severe asthma. |
topic |
asthma biomarkers saliva amphiregulin (AREG) non-invasive |
url |
https://www.frontiersin.org/articles/10.3389/fmed.2020.561866/full |
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doaj-94c010a658d4400d811bd6968daadf232020-11-25T04:03:46ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-10-01710.3389/fmed.2020.561866561866Blood and Salivary Amphiregulin Levels as Biomarkers for AsthmaMahmood Yaseen Hachim0Mahmood Yaseen Hachim1Noha Mousaad Elemam2Rakhee K. Ramakrishnan3Laila Salameh4Ronald Olivenstein5Ibrahim Yaseen Hachim6Ibrahim Yaseen Hachim7Thenmozhi Venkatachalam8Bassam Mahboub9Bassam Mahboub10Saba Al Heialy11Saba Al Heialy12Rabih Halwani13Rabih Halwani14Qutayba Hamid15Qutayba Hamid16Qutayba Hamid17Rifat Hamoudi18Rifat Hamoudi19Rifat Hamoudi20College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesRashid Hospital, Dubai Health Authority, Dubai, United Arab EmiratesMeakins-Christie Laboratories, McGill University, Montreal, QC, CanadaSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesRashid Hospital, Dubai Health Authority, Dubai, United Arab EmiratesDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesCollege of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab EmiratesMeakins-Christie Laboratories, McGill University, Montreal, QC, CanadaSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesMeakins-Christie Laboratories, McGill University, Montreal, QC, CanadaDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesDivision of Surgery and Interventional Science, UCL, London, United KingdomBackground: Amphiregulin (AREG) expression in asthmatic airways and sputum was shown to increase and correlate with asthma. However, no studies were carried out to evaluate the AREG level in blood and saliva of asthmatic patients.Objective: To measure circulating AREG mRNA and protein concentrations in blood, saliva, and bronchial biopsies samples from asthmatic patients.Methods: Plasma and Saliva AREG protein concentrations were measured using ELISA while PBMCs, and Saliva mRNA expression was measured by RT qPCR in non-severe, and severe asthmatic patients compared to healthy controls. Primary asthmatic bronchial epithelial cells and fibroblasts were assessed for AREG mRNA expression and released soluble AREG in their conditioned media. Tissue expression of AREG was evaluated using immunohistochemistry of bronchial biopsies from asthmatic patients and healthy controls. Publicly available transcriptomic databases were explored for the global transcriptomic profile of bronchial epithelium, and PBMCs were explored for AREG expression in asthmatic vs. healthy controls.Results: Asthmatic patients had higher AREG protein levels in blood and saliva compared to control subjects. Higher mRNA expression in saliva and primary bronchial epithelial cells plus higher AREG immunoreactivity in bronchial biopsies were also observed. Both blood and saliva AREG levels showed positive correlations with allergic rhinitis status, atopy status, eczema status, plasma periostin, neutrophilia, Montelukast sodium use, ACT score, FEV1, and FEV1/FVC. In silico analysis showed that severe asthmatic bronchial epithelium with high AREG gene expression is associated with higher neutrophils infiltration.Conclusion: AREG levels measured in a minimally invasive blood sample and a non-invasive saliva sample are higher in non-allergic severe asthma.Clinical ImplicationsThis is the first report to show the higher level of AREG levels in blood and saliva of non-allergic severe asthma.https://www.frontiersin.org/articles/10.3389/fmed.2020.561866/fullasthmabiomarkerssalivaamphiregulin (AREG)non-invasive |