Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma.

Adult Aged Antibodies, Monoclonal, Humanized / therapeutic use Asthma / drug therapy Bronchi / immunology Dermatitis, Atopic / drug therapy Dermatologic Agents / therapeutic use Female Humans Immunoglobulin E / blood Interleukins / antagonists & inhibitors Male Middle Aged Neutrophils / drug effects Proteome / drug effects Severity of Illness Index Skin / immunology Sputum / immunology Transcriptome / drug effects Treatment Outcome Interleukin-22

Fezakinumab IL-22 atopic dermatitis gene set variation analysis severe asthma

Journal

The Journal of allergy and clinical immunology

ISSN: 1097-6825

Titre abrégé: J Allergy Clin Immunol

Pays: United States

ID NLM: 1275002

Informations de publication

Date de publication:
01 2022

Historique:

received: 12 11 2020

revised: 11 03 2021

accepted: 09 04 2021

pubmed: 24 4 2021

medline: 4 3 2022

entrez: 23 4 2021

Statut: ppublish

Résumé

Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases. 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. 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. The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, T 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.

Sections du résumé

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, T

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.

Identifiants

DOI: 10.1016/j.jaci.2021.04.010 PMID: 33891981

pubmed: 33891981

pii: S0091-6749(21)00648-5

doi: 10.1016/j.jaci.2021.04.010

pii:

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

Dermatologic Agents 0

Interleukins 0

Proteome 0

fezakinumab 0S77U25XZ3

Immunoglobulin E 37341-29-0

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

89-101

Subventions

Organisme : Biotechnology and Biological Sciences Research Council

ID : BIDS3000032503

Pays : United Kingdom

Commentaires et corrections

Type : CommentIn