Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma

Frontiers in Medicine

article

Mahmood Yaseen Hachim¹  Rabih Halwani³  Qutayba Hamid²  Rifat Hamoudi²  Noha Mousaad Elemam²  Rakhee K. Ramakrishnan²  Laila Salameh⁶  Ronald Olivenstein⁴  Ibrahim Yaseen Hachim²  Thenmozhi Venkatachalam²  Bassam Mahboub³  Saba Al Heialy¹ 

[1] College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, United Arab Emirates;Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, United Arab Emirates;Department of Clinical Sciences, College of Medicine, University of Sharjah, United Arab Emirates;Meakins-Christie Laboratories, McGill University;Division of Surgery and Interventional Science, United Kingdom;Rashid Hospital, Dubai Health Authority, United Arab Emirates

关键词: asthma;    biomarkers;    saliva;    amphiregulin (AREG);    non-invasive;   

DOI  :  10.3389/fmed.2020.561866

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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 Implications This is the first report to show the higher level of AREG levels in blood and saliva of non-allergic severe asthma.

【 授权许可】

CC BY