Early mucosal type 1 immunity in pre-school wheezers as protective factor for development of asthma at school-age 3090

Abstract Description Allergy and asthma are defined by local type-2 immunity at the airway barrier. However, whether immunity type-specific epithelial phenotypes can predict the persistence of asthma at school-age, remains elusive. We analyzed nasal immunophenotypes (nasotypes; NT) by nasal transcriptomics from 265 children (79 healthy, 81 wheezers, 105 asthmatic) from the ALL-Age Asthma Cohort (ALLIANCE; DZL), median age 10.4 [1.1-20.3]. E-signatures were assigned in single-cell transcriptomics (scRNASeq) of primary 3D-airway cultures. Correlation analysis of secreted genes showed antagonistic expression between IFNG-correlated E1-NT (IDO,CSF3,CCL20), IL4-correlated E2-NT (POSTN,CCL26,CST1) and IL17C-correlated E3-NT (IL36G,KLK7,KRTDAP). E1/E2/E3 transcriptional programs were assigned to distinct cells in scRNASeq. E2-NT was highly expressed in asthmatic children (age>6) and correlated with type-2 parameters (total/specific IgE, FeNO, eosinophilia). Wheezers showed an early E1/E3-signature (age 1-3; N = 36), while E2-signature was activated from age 4 (N = 38). Multivariate models adjusted for sensitization and age (AUC=0.87) revealed E1-NT as protective (OR = 0.29;P<0.05) and E3-NT as risk factor (OR = 2.03;P<0.05) for asthma development at age 6. The assessment of the here identified three nasotypes, activated age- and disease-dependently, predicted to a high degree (AUC=0.87) the persistence of asthma with E1 showing protection from progression, but E3 independently predicting progression of disease. Funding Sources Supported by the German Center of Lung Research (DZL) funded by the Federal Ministry of Education and Research (BMBF), the Bavarian State Office for Health and Food Safety (LGL; K1-2497-GLB-20-V4) of the Bavarian State Ministry of Health and Care and by grants from Deutsche Forschungsgemeinschaft RTG2668 (Project A5, Project-ID: 435874434) to C.B. Schmidt-Weber. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)

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Journal
The Journal of Immunology
Published
2025-11-01
DOI
https://doi.org/10.1093/jimmun/vkaf283.928
Primary Topic
Asthma and respiratory diseases
Type
article
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article

Early mucosal type 1 immunity in pre-school wheezers as protective factor for development of asthma at school-age 3090

Benjamin Schubert, Thomas Bahmer, Svenja Foth, Tobias Trojan et al.
The Journal of Immunology
Asthma and respiratory diseases
article

Early mucosal type 1 immunity in pre-school wheezers as protective factor for development of asthma at school-age 3090

Benjamin Schubert, Thomas Bahmer, Svenja Foth, Tobias Trojan, Folke Brinkmann, Anna Erb, Maren Büttner, Matthias Kopp, Ruth Grychtol, Klaus F. Rabe, Nicole Maison, Anna‐Maria Dittrich, Erika von Mutius, Adam Chaker, Ulrich M. Zissler, Bianca Schaub, Sabina Illi, Constanze A. Jakwerth, Markus Weckmann, Felix Drost, Silke van Koningsbruggen‐Rietschel, Jimmy Omony, Chrysanthi Skevaki, Martin Feuerherd, Carsten B. Schmidt‐Weber, A. Gabr, Ulrike Protzer, Helen Charles, Gesine Hansen, Madlen Oelsner
article en

Abstract

Abstract Description Allergy and asthma are defined by local type-2 immunity at the airway barrier. However, whether immunity type-specific epithelial phenotypes can predict the persistence of asthma at school-age, remains elusive. We analyzed nasal immunophenotypes (nasotypes; NT) by nasal transcriptomics from 265 children (79 healthy, 81 wheezers, 105 asthmatic) from the ALL-Age Asthma Cohort (ALLIANCE; DZL), median age 10.4 [1.1-20.3]. E-signatures were assigned in single-cell transcriptomics (scRNASeq) of primary 3D-airway cultures. Correlation analysis of secreted genes showed antagonistic expression between IFNG-correlated E1-NT (IDO,CSF3,CCL20), IL4-correlated E2-NT (POSTN,CCL26,CST1) and IL17C-correlated E3-NT (IL36G,KLK7,KRTDAP). E1/E2/E3 transcriptional programs were assigned to distinct cells in scRNASeq. E2-NT was highly expressed in asthmatic children (age>6) and correlated with type-2 parameters (total/specific IgE, FeNO, eosinophilia). Wheezers showed an early E1/E3-signature (age 1-3; N = 36), while E2-signature was activated from age 4 (N = 38). Multivariate models adjusted for sensitization and age (AUC=0.87) revealed E1-NT as protective (OR = 0.29;P<0.05) and E3-NT as risk factor (OR = 2.03;P<0.05) for asthma development at age 6. The assessment of the here identified three nasotypes, activated age- and disease-dependently, predicted to a high degree (AUC=0.87) the persistence of asthma with E1 showing protection from progression, but E3 independently predicting progression of disease. Funding Sources Supported by the German Center of Lung Research (DZL) funded by the Federal Ministry of Education and Research (BMBF), the Bavarian State Office for Health and Food Safety (LGL; K1-2497-GLB-20-V4) of the Bavarian State Ministry of Health and Care and by grants from Deutsche Forschungsgemeinschaft RTG2668 (Project A5, Project-ID: 435874434) to C.B. Schmidt-Weber. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)

The Journal of ImmunologyVol. 214(Supplement_1)
Helmholtz Association of German Research Centres (DE), Philipps University of Marburg (DE), TUM Klinikum (DE), Helmholtz Zentrum München (DE), Medizinische Hochschule Hannover (DE), University Children’s Hospital Bern (CH), German Center for Lung Research (DE), Universities of Giessen and Marburg Lung Center (DE), University Hospital Cologne (DE), Ludwig-Maximilians-Universität München (DE)
Openalex Percentile: Top 56%
Asthma and respiratory diseases
DOIOpen Access PDFOpenAlex
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