{"title":"Nasal brushing molecular endotyping distinguishes patients with chronic rhinosinusitis with nasal polyps with better response to dupilumab","authors":"","doi":"10.1016/j.jaci.2024.05.030","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>There is evidence of pathophysiologic diversity in chronic rhinosinusitis with nasal polyps (CRSwNP), but data characterizing the molecular endotypes of CRSwNP and their association with treatment are lacking.</p></div><div><h3>Objective</h3><p>This study aimed to identify gene signatures associated with CRSwNP endotypes, clinical features, and dupilumab treatment response.</p></div><div><h3>Methods</h3><p>Nasal brushing samples were collected from 89 patients randomized to dupilumab 300 mg every 2 weeks or placebo in the SINUS-52 trial (NCT02898454). Microarrays were used to identify transcriptional clusters and assess the relationship between gene expression and baseline clinical features and clinical response to dupilumab. Endotype signatures were determined using differential expression analysis.</p></div><div><h3>Results</h3><p>Two distinct transcriptional clusters (C1 and C2) were identified, both with elevated type 2 biomarkers. At baseline, C2 patients had higher mean Nasal Polyp Score and higher type 2 biomarker levels than C1 patients. At week 24, significant improvements in clinical outcomes (dupilumab vs placebo) were observed in both clusters, although the magnitude of improvements was significantly greater in C2 than in C1, and more C2 patients demonstrated clinically meaningful responses. Gene set enrichment analysis supported the existence of 2 molecular endotypes: C2 was enriched in genes associated with type 2 inflammation (including periostin, cadherin-26, and type 2 cysteine protease inhibitors), while C1 was enriched in genes associated with T cell activation and IL-12 production.</p></div><div><h3>Conclusions</h3><p>Two distinct gene signatures associated with CRSwNP clinical features were identified; the endotype signatures were associated with clinical outcome measures and magnitude of dupilumab response.</p></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091674924006067/pdfft?md5=837b2e8847a542981f2dd871fc059c3f&pid=1-s2.0-S0091674924006067-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091674924006067","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
There is evidence of pathophysiologic diversity in chronic rhinosinusitis with nasal polyps (CRSwNP), but data characterizing the molecular endotypes of CRSwNP and their association with treatment are lacking.
Objective
This study aimed to identify gene signatures associated with CRSwNP endotypes, clinical features, and dupilumab treatment response.
Methods
Nasal brushing samples were collected from 89 patients randomized to dupilumab 300 mg every 2 weeks or placebo in the SINUS-52 trial (NCT02898454). Microarrays were used to identify transcriptional clusters and assess the relationship between gene expression and baseline clinical features and clinical response to dupilumab. Endotype signatures were determined using differential expression analysis.
Results
Two distinct transcriptional clusters (C1 and C2) were identified, both with elevated type 2 biomarkers. At baseline, C2 patients had higher mean Nasal Polyp Score and higher type 2 biomarker levels than C1 patients. At week 24, significant improvements in clinical outcomes (dupilumab vs placebo) were observed in both clusters, although the magnitude of improvements was significantly greater in C2 than in C1, and more C2 patients demonstrated clinically meaningful responses. Gene set enrichment analysis supported the existence of 2 molecular endotypes: C2 was enriched in genes associated with type 2 inflammation (including periostin, cadherin-26, and type 2 cysteine protease inhibitors), while C1 was enriched in genes associated with T cell activation and IL-12 production.
Conclusions
Two distinct gene signatures associated with CRSwNP clinical features were identified; the endotype signatures were associated with clinical outcome measures and magnitude of dupilumab response.
期刊介绍:
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.