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SHR Neuro Cancer Cardio Lipid Metab Microb

Badi, YE; Pavel, AB; Pavlidis, S; Riley, JH; Bates, S; Kermani, NZ; Knowles, R; Kolmert, J; Wheelock, CE; Worsley, S; Uddin, M; Alving, K; Bakke, PS; Behndig, A; Caruso, M; Chanez, P; Fleming, LJ; Fowler, SJ; Frey, U; Howarth, P; Horváth, I; Krug, N; Maitland-van, der, Zee, AH; Montuschi, P; Roberts, G; Sanak, M; Shaw, DE; Singer, F; Sterk, PJ; Djukanovic, R; Dahlen, SE; Guo, YK; Chung, KF; Guttman-Yassky, E; Adcock, IM, , U-BIOPRED, Study, Group.
Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma.
J Allergy Clin Immunol. 2022; 149(1):89-101 Doi: 10.1016/j.jaci.2021.04.010
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Singer Florian
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Adult - administration & dosage
Aged - administration & dosage
Antibodies, Monoclonal, Humanized - therapeutic use
Asthma - drug therapy, genetics, immunology
Bronchi - immunology
Dermatitis, Atopic - drug therapy, genetics, immunology
Dermatologic Agents - therapeutic use
Female - administration & dosage
Humans - administration & dosage
Immunoglobulin E - blood
Interleukins - antagonists & inhibitors, genetics, immunology
Male - administration & dosage
Middle Aged - administration & dosage
Neutrophils - drug effects, immunology
Proteome - drug effects
Severity of Illness Index - administration & dosage
Skin - immunology
Sputum - immunology
Transcriptome - drug effects
Treatment Outcome - administration & dosage

Find related publications in this database (Keywords)
Fezakinumab
atopic dermatitis
gene set variation analysis
IL-22
severe asthma
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