Cargando…
Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma
Asthma is a chronic inflammatory disorder of the airways. Disease presentation varies greatly in terms of cause, development, severity, and response to medication, and thus the condition has been subdivided into a number of asthma phenotypes. There is still an unmet need for the identification of ph...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586825/ https://www.ncbi.nlm.nih.gov/pubmed/31221987 http://dx.doi.org/10.1038/s41598-019-45257-1 |
_version_ | 1783428951615471616 |
---|---|
author | Whittle, E. Leonard, M. O. Gant, T. W. Tonge, D. P |
author_facet | Whittle, E. Leonard, M. O. Gant, T. W. Tonge, D. P |
author_sort | Whittle, E. |
collection | PubMed |
description | Asthma is a chronic inflammatory disorder of the airways. Disease presentation varies greatly in terms of cause, development, severity, and response to medication, and thus the condition has been subdivided into a number of asthma phenotypes. There is still an unmet need for the identification of phenotype-specific markers and accompanying molecular tools that facilitate the classification of asthma phenotype. To this end, we utilised a range of molecular tools to characterise a well-defined group of female adults with poorly controlled atopic asthma associated with house dust mite (HDM) allergy, relative to non-asthmatic control subjects. Circulating messenger RNA (mRNA) and microRNA (miRNA) were sequenced and quantified, and a differential expression analysis of the two RNA populations performed to determine how gene expression and regulation varied in the disease state. Further, a number of circulating proteins (IL-4, 5, 10, 13, 17 A, Eotaxin, GM-CSF, IFNy, MCP-1, TARC, TNFα, Total IgE, and Endotoxin) were quantified to determine whether the protein profiles differed significantly dependent on disease state. Finally, we utilised a previously published assessment of the circulating “blood microbiome” performed using 16S rRNA amplification and sequencing. Asthmatic subjects displayed a range of significant alterations to circulating gene expression and regulation, relative to healthy control subjects, that may influence systemic immune activity. Notably, several circulating mRNAs were detected in just the asthma group or just in the control group, and many more were observed to be expressed at significantly different levels in the asthma group compared to the control group. Proteomic analysis revealed increased levels of inflammatory proteins within the serum, and decreased levels of the bacterial endotoxin protein in the asthmatic state. Comparison of blood microbiome composition revealed a significant increase in the Firmicutes phylum with asthma that was associated with a concomitant reduction in the Proteobacteria phylum. This study provides a valuable insight into the systemic changes evident in the HDM-associated asthma, identifies a range of molecules that are present in the circulation in a condition-specific manner (with clear biomarker potential), and highlights a range of hypotheses for further study. |
format | Online Article Text |
id | pubmed-6586825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65868252019-06-27 Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma Whittle, E. Leonard, M. O. Gant, T. W. Tonge, D. P Sci Rep Article Asthma is a chronic inflammatory disorder of the airways. Disease presentation varies greatly in terms of cause, development, severity, and response to medication, and thus the condition has been subdivided into a number of asthma phenotypes. There is still an unmet need for the identification of phenotype-specific markers and accompanying molecular tools that facilitate the classification of asthma phenotype. To this end, we utilised a range of molecular tools to characterise a well-defined group of female adults with poorly controlled atopic asthma associated with house dust mite (HDM) allergy, relative to non-asthmatic control subjects. Circulating messenger RNA (mRNA) and microRNA (miRNA) were sequenced and quantified, and a differential expression analysis of the two RNA populations performed to determine how gene expression and regulation varied in the disease state. Further, a number of circulating proteins (IL-4, 5, 10, 13, 17 A, Eotaxin, GM-CSF, IFNy, MCP-1, TARC, TNFα, Total IgE, and Endotoxin) were quantified to determine whether the protein profiles differed significantly dependent on disease state. Finally, we utilised a previously published assessment of the circulating “blood microbiome” performed using 16S rRNA amplification and sequencing. Asthmatic subjects displayed a range of significant alterations to circulating gene expression and regulation, relative to healthy control subjects, that may influence systemic immune activity. Notably, several circulating mRNAs were detected in just the asthma group or just in the control group, and many more were observed to be expressed at significantly different levels in the asthma group compared to the control group. Proteomic analysis revealed increased levels of inflammatory proteins within the serum, and decreased levels of the bacterial endotoxin protein in the asthmatic state. Comparison of blood microbiome composition revealed a significant increase in the Firmicutes phylum with asthma that was associated with a concomitant reduction in the Proteobacteria phylum. This study provides a valuable insight into the systemic changes evident in the HDM-associated asthma, identifies a range of molecules that are present in the circulation in a condition-specific manner (with clear biomarker potential), and highlights a range of hypotheses for further study. Nature Publishing Group UK 2019-06-20 /pmc/articles/PMC6586825/ /pubmed/31221987 http://dx.doi.org/10.1038/s41598-019-45257-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Whittle, E. Leonard, M. O. Gant, T. W. Tonge, D. P Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma |
title | Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma |
title_full | Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma |
title_fullStr | Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma |
title_full_unstemmed | Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma |
title_short | Multi-Method Molecular Characterisation of Human Dust-Mite-associated Allergic Asthma |
title_sort | multi-method molecular characterisation of human dust-mite-associated allergic asthma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586825/ https://www.ncbi.nlm.nih.gov/pubmed/31221987 http://dx.doi.org/10.1038/s41598-019-45257-1 |
work_keys_str_mv | AT whittlee multimethodmolecularcharacterisationofhumandustmiteassociatedallergicasthma AT leonardmo multimethodmolecularcharacterisationofhumandustmiteassociatedallergicasthma AT ganttw multimethodmolecularcharacterisationofhumandustmiteassociatedallergicasthma AT tongedp multimethodmolecularcharacterisationofhumandustmiteassociatedallergicasthma |