Imperial College London
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DrLouiseFleming

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 2938l.fleming

 
 
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Location

 

Department of Respiratory PaediaRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Badi:2022:10.1016/j.jaci.2021.04.010,
author = {Badi, Y and Pavel, AB and Pavlidis, S and Riley, J and Bates, S and Zounemat, Kermani N and Knowles, R and Kolmert, J and Wheelock, C and Worsley, S and Uddin, M and Alving, K and Bakke, P and Behndig, A and Caruso, M and Chanez, P and Fleming, L and Fowler, S and Frey, U and Howarth, P and Horvath, I and Krug, N and Maitland, van der Zee A and Montuschi, P and Roberts, G and Sanak, M and Shaw, D and Singer, F and Sterk, P and Djukanovic, R and Dahlen, S-E and Guo, Y and Chung, KF and Guttman-Yassky, E and Adcock, IM and on, behalf of theU-BIOPRED Study Group and Adcock, I and Badi, Y and Pavel, AB and Pavlidis, S and riley, J and bates, S and Zounemat, Kermani N and Knowles, R and kolmert, J and wheelock, C and worsley, S and uddin, M and alving, K and bakke, P and Behndig, A and Caruso, M and Chanez, P and Fleming, L and Fowler, S and Frey, U and Howarth, P and Horvath, I and Krug, N and Maitland, van der Zee A and Montuschi, P and Roberts, G and Sanak, M and Shaw, D and Singer, F an},
doi = {10.1016/j.jaci.2021.04.010},
journal = {Journal of Allergy and Clinical Immunology},
pages = {89--101},
title = {Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma},
url = {http://dx.doi.org/10.1016/j.jaci.2021.04.010},
volume = {149},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective:We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods:An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results:The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P < .05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P < .05) and particularly in neutrophilic and mixed granulocytic sputum (P < .05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions:The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
AU  - Badi,Y
AU  - Pavel,AB
AU  - Pavlidis,S
AU  - Riley,J
AU  - Bates,S
AU  - Zounemat,Kermani N
AU  - Knowles,R
AU  - Kolmert,J
AU  - Wheelock,C
AU  - Worsley,S
AU  - Uddin,M
AU  - Alving,K
AU  - Bakke,P
AU  - Behndig,A
AU  - Caruso,M
AU  - Chanez,P
AU  - Fleming,L
AU  - Fowler,S
AU  - Frey,U
AU  - Howarth,P
AU  - Horvath,I
AU  - Krug,N
AU  - Maitland,van der Zee A
AU  - Montuschi,P
AU  - Roberts,G
AU  - Sanak,M
AU  - Shaw,D
AU  - Singer,F
AU  - Sterk,P
AU  - Djukanovic,R
AU  - Dahlen,S-E
AU  - Guo,Y
AU  - Chung,KF
AU  - Guttman-Yassky,E
AU  - Adcock,IM
AU  - on,behalf of theU-BIOPRED Study Group
AU  - Adcock,I
AU  - Badi,Y
AU  - Pavel,AB
AU  - Pavlidis,S
AU  - riley,J
AU  - bates,S
AU  - Zounemat,Kermani N
AU  - Knowles,R
AU  - kolmert,J
AU  - wheelock,C
AU  - worsley,S
AU  - uddin,M
AU  - alving,K
AU  - bakke,P
AU  - Behndig,A
AU  - Caruso,M
AU  - Chanez,P
AU  - Fleming,L
AU  - Fowler,S
AU  - Frey,U
AU  - Howarth,P
AU  - Horvath,I
AU  - Krug,N
AU  - Maitland,van der Zee A
AU  - Montuschi,P
AU  - Roberts,G
AU  - Sanak,M
AU  - Shaw,D
AU  - Singer,F
AU  - Sterk,P
AU  - Djukanovic,R
AU  - Dahlen,S-E
AU  - Guo,Y
AU  - Chung,KF
AU  - Guttman-Yassky,E
DO  - 10.1016/j.jaci.2021.04.010
EP  - 101
PY  - 2022///
SN  - 0091-6749
SP  - 89
TI  - Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2021.04.010
UR  - http://hdl.handle.net/10044/1/89510
VL  - 149
ER  -
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