BibTex format
@article{Rossios:2017:10.1016/j.jaci.2017.02.045,
author = {Rossios, C and Pavlidis, S and Hoda, U and Kuo, CH and Wiegman, C and Russell, K and Sun, K and Loza, MJ and Baribaud, F and Durham, AL and Ojo, O and Lutter, R and Rowe, A and Bansal, A and Auffray, C and Sousa, A and Corfield, J and Djukanovic, R and Guo, Y and Sterk, PJ and Chung, KF and Adcock, IM and Unbiased, Biomarkers for the Prediction of Respiratory Diseases Outcomes U-BIOPRED Consortia Project Team},
doi = {10.1016/j.jaci.2017.02.045},
journal = {Journal of Allergy and Clinical Immunology},
pages = {560--570},
title = {Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma},
url = {http://dx.doi.org/10.1016/j.jaci.2017.02.045},
volume = {141},
year = {2017}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Sputum analysis in asthmatic patients is used to define airway inflammatory processes and might guide therapy. 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. 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. 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 inflammati
AU - Rossios,C
AU - Pavlidis,S
AU - Hoda,U
AU - Kuo,CH
AU - Wiegman,C
AU - Russell,K
AU - Sun,K
AU - Loza,MJ
AU - Baribaud,F
AU - Durham,AL
AU - Ojo,O
AU - Lutter,R
AU - Rowe,A
AU - Bansal,A
AU - Auffray,C
AU - Sousa,A
AU - Corfield,J
AU - Djukanovic,R
AU - Guo,Y
AU - Sterk,PJ
AU - Chung,KF
AU - Adcock,IM
AU - Unbiased,Biomarkers for the Prediction of Respiratory Diseases Outcomes U-BIOPRED Consortia Project Team
DO - 10.1016/j.jaci.2017.02.045
EP - 570
PY - 2017///
SN - 1097-6825
SP - 560
TI - Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma
T2 - Journal of Allergy and Clinical Immunology
UR - http://dx.doi.org/10.1016/j.jaci.2017.02.045
UR - https://www.sciencedirect.com/science/article/pii/S0091674917307649?via%3Dihub
UR - http://hdl.handle.net/10044/1/49132
VL - 141
ER -
