K Milger1,2,3, J Götschke1,2,3, L Krause4, P Nathan2,3, F Alessandrini2,5, A Tufman1,2, R Fischer6, S Bartel2,7,8, F J Theis4,9, J Behr1,2, S Dehmel2,3, N S Mueller4, N Kneidinger1,2, S Krauss-Etschmann2,3,7,8,10. 1. Department of Internal Medicine V, Comprehensive Pneumology Center, University of Munich, Munich, Germany. 2. Member of the German Center for Lung Research (DZL), Munich, Germany. 3. Institute of Lung Biology and Disease (ILBD), Helmholtz Center Munich, Comprehensive Pneumology Center (CPC-M), Munich, Germany. 4. Institute of Computational Biology, Helmholtz Center Munich, Munich, Germany. 5. Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany. 6. Pneumologische Praxis München-Pasing, Munich, Germany. 7. Early origins of chronic lung disease, Priority Area Asthma and Allergy, Research Center Borstel, Borstel, Germany. 8. Airway Research Center North (ARCN), Borstel, Germany. 9. Department of Mathematics, Technical University of Munich, Garching, Germany. 10. Institute of Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
Abstract
BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach. METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.
BACKGROUND:Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and humanasthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach. METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthmapatients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthmapatients and 12 healthy controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in humanallergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.
Authors: Li Guo; Yongsheng Li; Kara M Cirillo; Robert A Marick; Zhe Su; Xing Yin; Xu Hua; Gordon B Mills; Nidhi Sahni; S Stephen Yi Journal: Brief Bioinform Date: 2021-09-02 Impact factor: 11.622
Authors: Sara Nunes; Icaro Bonyek Silva; Mariana Rosa Ampuero; Almério Libório Lopes de Noronha; Lígia Correia Lima de Souza; Thaizza Cavalcante Correia; Ricardo Khouri; Viviane Sampaio Boaventura; Aldina Barral; Pablo Ivan Pereira Ramos; Cláudia Brodskyn; Pablo Rafael Silveira Oliveira; Natalia Machado Tavares Journal: Front Immunol Date: 2018-04-04 Impact factor: 7.561
Authors: J Bousquet; C A Akdis; C Grattan; P A Eigenmann; K Hoffmann-Sommergruber; P W Hellings; I Agache Journal: Clin Transl Allergy Date: 2018-11-27 Impact factor: 5.871