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Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma.

Identifieur interne : 000C76 ( PubMed/Corpus ); précédent : 000C75; suivant : 000C77

Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma.

Auteurs : Christos Rossios ; Stelios Pavlidis ; Uruj Hoda ; Chih-Hsi Kuo ; Coen Wiegman ; Kirsty Russell ; Kai Sun ; Matthew J. Loza ; Frederic Baribaud ; Andrew L. Durham ; Oluwaseun Ojo ; Rene Lutter ; Anthony Rowe ; Aruna Bansal ; Charles Auffray ; Ana Sousa ; Julie Corfield ; Ratko Djukanovic ; Yike Guo ; Peter J. Sterk ; Kian Fan Chung ; Ian M. Adcock

Source :

RBID : pubmed:28528200

Abstract

Sputum analysis in asthmatic patients is used to define airway inflammatory processes and might guide therapy.

DOI: 10.1016/j.jaci.2017.02.045
PubMed: 28528200

Links to Exploration step

pubmed:28528200

Le document en format XML

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<name sortKey="Guo, Yike" sort="Guo, Yike" uniqKey="Guo Y" first="Yike" last="Guo">Yike Guo</name>
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<name sortKey="Sterk, Peter J" sort="Sterk, Peter J" uniqKey="Sterk P" first="Peter J" last="Sterk">Peter J. Sterk</name>
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<nlm:affiliation>Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands.</nlm:affiliation>
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<name sortKey="Chung, Kian Fan" sort="Chung, Kian Fan" uniqKey="Chung K" first="Kian Fan" last="Chung">Kian Fan Chung</name>
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<name sortKey="Adcock, Ian M" sort="Adcock, Ian M" uniqKey="Adcock I" first="Ian M" last="Adcock">Ian M. Adcock</name>
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<nlm:affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom; Janssen Research and Development, High Wycombe, United Kingdom.</nlm:affiliation>
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<name sortKey="Hoda, Uruj" sort="Hoda, Uruj" uniqKey="Hoda U" first="Uruj" last="Hoda">Uruj Hoda</name>
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<name sortKey="Kuo, Chih Hsi" sort="Kuo, Chih Hsi" uniqKey="Kuo C" first="Chih-Hsi" last="Kuo">Chih-Hsi Kuo</name>
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<nlm:affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom.</nlm:affiliation>
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<name sortKey="Wiegman, Coen" sort="Wiegman, Coen" uniqKey="Wiegman C" first="Coen" last="Wiegman">Coen Wiegman</name>
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<nlm:affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</nlm:affiliation>
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<name sortKey="Russell, Kirsty" sort="Russell, Kirsty" uniqKey="Russell K" first="Kirsty" last="Russell">Kirsty Russell</name>
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<nlm:affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</nlm:affiliation>
</affiliation>
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<name sortKey="Sun, Kai" sort="Sun, Kai" uniqKey="Sun K" first="Kai" last="Sun">Kai Sun</name>
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<nlm:affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom.</nlm:affiliation>
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<name sortKey="Loza, Matthew J" sort="Loza, Matthew J" uniqKey="Loza M" first="Matthew J" last="Loza">Matthew J. Loza</name>
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<nlm:affiliation>Janssen Research and Development, High Wycombe, United Kingdom.</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Baribaud, Frederic" sort="Baribaud, Frederic" uniqKey="Baribaud F" first="Frederic" last="Baribaud">Frederic Baribaud</name>
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<nlm:affiliation>Janssen Research and Development, High Wycombe, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Durham, Andrew L" sort="Durham, Andrew L" uniqKey="Durham A" first="Andrew L" last="Durham">Andrew L. Durham</name>
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<nlm:affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Ojo, Oluwaseun" sort="Ojo, Oluwaseun" uniqKey="Ojo O" first="Oluwaseun" last="Ojo">Oluwaseun Ojo</name>
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<nlm:affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Lutter, Rene" sort="Lutter, Rene" uniqKey="Lutter R" first="Rene" last="Lutter">Rene Lutter</name>
<affiliation>
<nlm:affiliation>Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Rowe, Anthony" sort="Rowe, Anthony" uniqKey="Rowe A" first="Anthony" last="Rowe">Anthony Rowe</name>
<affiliation>
<nlm:affiliation>Janssen Research and Development, High Wycombe, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bansal, Aruna" sort="Bansal, Aruna" uniqKey="Bansal A" first="Aruna" last="Bansal">Aruna Bansal</name>
<affiliation>
<nlm:affiliation>Acclarogen, St John's Innovation Centre, Cambridge, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Auffray, Charles" sort="Auffray, Charles" uniqKey="Auffray C" first="Charles" last="Auffray">Charles Auffray</name>
<affiliation>
<nlm:affiliation>European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Sousa, Ana" sort="Sousa, Ana" uniqKey="Sousa A" first="Ana" last="Sousa">Ana Sousa</name>
<affiliation>
<nlm:affiliation>Respiratory Therapeutic Unit, GSK, Stockley Park, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Corfield, Julie" sort="Corfield, Julie" uniqKey="Corfield J" first="Julie" last="Corfield">Julie Corfield</name>
<affiliation>
<nlm:affiliation>AstraZeneca R&D, Molndal, Sweden, and Areteva R&D, Nottingham, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Djukanovic, Ratko" sort="Djukanovic, Ratko" uniqKey="Djukanovic R" first="Ratko" last="Djukanovic">Ratko Djukanovic</name>
<affiliation>
<nlm:affiliation>Faculty of Medicine, Southampton University, and the NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Guo, Yike" sort="Guo, Yike" uniqKey="Guo Y" first="Yike" last="Guo">Yike Guo</name>
<affiliation>
<nlm:affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Sterk, Peter J" sort="Sterk, Peter J" uniqKey="Sterk P" first="Peter J" last="Sterk">Peter J. Sterk</name>
<affiliation>
<nlm:affiliation>Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Chung, Kian Fan" sort="Chung, Kian Fan" uniqKey="Chung K" first="Kian Fan" last="Chung">Kian Fan Chung</name>
<affiliation>
<nlm:affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Adcock, Ian M" sort="Adcock, Ian M" uniqKey="Adcock I" first="Ian M" last="Adcock">Ian M. Adcock</name>
<affiliation>
<nlm:affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia. Electronic address: ian.adcock@imperial.ac.uk.</nlm:affiliation>
</affiliation>
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<series>
<title level="j">The Journal of allergy and clinical immunology</title>
<idno type="eISSN">1097-6825</idno>
<imprint>
<date when="2017" type="published">2017</date>
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<front>
<div type="abstract" xml:lang="en">Sputum analysis in asthmatic patients is used to define airway inflammatory processes and might guide therapy.</div>
</front>
</TEI>
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<PMID Version="1">28528200</PMID>
<DateCreated>
<Year>2017</Year>
<Month>05</Month>
<Day>21</Day>
</DateCreated>
<DateRevised>
<Year>2017</Year>
<Month>06</Month>
<Day>18</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1097-6825</ISSN>
<JournalIssue CitedMedium="Internet">
<PubDate>
<Year>2017</Year>
<Month>May</Month>
<Day>18</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of allergy and clinical immunology</Title>
<ISOAbbreviation>J. Allergy Clin. Immunol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">S0091-6749(17)30764-9</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jaci.2017.02.045</ELocationID>
<Abstract>
<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Sputum analysis in asthmatic patients is used to define airway inflammatory processes and might guide therapy.</AbstractText>
<AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">We sought to determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared with nonsmoking patients with mild/moderate asthma.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">Induced sputum was obtained from nonsmoking patients with SA, smokers/ex-smokers with severe asthma, nonsmoking patients with mild/moderate asthma (MMAs), and healthy nonsmoking control subjects. Differential cell counts, microarray analysis of cell pellets, and SOMAscan analysis of sputum analytes were performed. CRID3 was used to inhibit the inflammasome in a mouse model of SA.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Eosinophilic and mixed neutrophilic/eosinophilic inflammation were more prevalent in patients with SA compared with MMAs. Forty-two genes probes were upregulated (>2-fold) in nonsmoking patients with severe asthma compared with MMAs, including IL-1 receptor (IL-1R) family and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NRLP3) inflammasome members (false discovery rate < 0.05). The inflammasome proteins nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 1 (NLRP1), NLRP3, and nucleotide-binding oligomerization domain (NOD)-like receptor C4 (NLRC4) were associated with neutrophilic asthma and with sputum IL-1β protein levels, whereas eosinophilic asthma was associated with an IL-13-induced TH2 signature and IL-1 receptor-like 1 (IL1RL1) mRNA expression. These differences were sputum specific because no activation of NLRP3 or enrichment of IL-1R family genes in bronchial brushings or biopsy specimens in patients with SA was observed. Expression of NLRP3 and of the IL-1R family genes was validated in the Airway Disease Endotyping for Personalized Therapeutics cohort. Inflammasome inhibition using CRID3 prevented airway hyperresponsiveness and airway inflammation (both neutrophilia and eosinophilia) in a mouse model of severe allergic asthma.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">IL1RL1 gene expression is associated with eosinophilic SA, whereas NLRP3 inflammasome expression is highest in patients with neutrophilic SA. TH2-driven eosinophilic inflammation and neutrophil-associated inflammasome activation might represent interacting pathways in patients with SA.</AbstractText>
<CopyrightInformation>Copyright © 2017. Published by Elsevier Inc.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Rossios</LastName>
<ForeName>Christos</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pavlidis</LastName>
<ForeName>Stelios</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom; Janssen Research and Development, High Wycombe, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Hoda</LastName>
<ForeName>Uruj</ForeName>
<Initials>U</Initials>
<AffiliationInfo>
<Affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Kuo</LastName>
<ForeName>Chih-Hsi</ForeName>
<Initials>CH</Initials>
<AffiliationInfo>
<Affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Wiegman</LastName>
<ForeName>Coen</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Russell</LastName>
<ForeName>Kirsty</ForeName>
<Initials>K</Initials>
<AffiliationInfo>
<Affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sun</LastName>
<ForeName>Kai</ForeName>
<Initials>K</Initials>
<AffiliationInfo>
<Affiliation>Department of Computing & Data Science Institute, Imperial College London, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Loza</LastName>
<ForeName>Matthew J</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo>
<Affiliation>Janssen Research and Development, High Wycombe, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Baribaud</LastName>
<ForeName>Frederic</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>Janssen Research and Development, High Wycombe, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Durham</LastName>
<ForeName>Andrew L</ForeName>
<Initials>AL</Initials>
<AffiliationInfo>
<Affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Ojo</LastName>
<ForeName>Oluwaseun</ForeName>
<Initials>O</Initials>
<AffiliationInfo>
<Affiliation>Airways Disease, National Heart & Lung Institute, Imperial College London, and the Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.</Affiliation>
</AffiliationInfo>
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<LastName>Lutter</LastName>
<ForeName>Rene</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Rowe</LastName>
<ForeName>Anthony</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Janssen Research and Development, High Wycombe, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Bansal</LastName>
<ForeName>Aruna</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Acclarogen, St John's Innovation Centre, Cambridge, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Auffray</LastName>
<ForeName>Charles</ForeName>
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