SEARCHCOHORTpediatrics, gastroenterology

cohort·pediatrics, gastroenterology, immunology, biomedical research, observational study·PMC10050742

Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches

Frontiers in Immunology · 15 authors, 8 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This study used transcriptomics, immune profiling, and metabolomics on esophageal biopsies and blood from 17 children with EoE and 15 controls to characterize local and systemic signatures.

Full summary

1,039 CHARS

The study conducted untargeted transcriptomics on esophageal biopsies, comprehensive immune analysis of biopsies and blood via flow cytometry, and non-targeted plasma metabolomics in children with EoE (n=17) versus controls (n=15). Transcriptomics revealed conserved immune dysregulation involving innate and adaptive pathways, epithelial barrier dysfunction, and perception of chemical stimuli. Immune analysis showed complex local inflammation with dysregulation of T1, T2, and T3 immunity. Systemically, an immune signature in blood was found, but non-targeted metabolomics more efficiently discriminated EoE, showing dysregulation of vitamin B6 and amino acid metabolism. Multi-omics integration suggested a plasma signature combining metabolomics and cytokines could serve as a diagnostic biomarker. Limitations include the small sample size and the need for validation in larger, independent cohorts. The findings support EoE as a complex disorder beyond T2 dysregulation and provide proof-of-concept for potential plasma biomarkers.

STUDY TYPE

cohort

SPECIALTY

pediatrics

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10050742

Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches

Frontiers in Immunology

READ THE FULL PAPER

ABSTRACT

Background Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers. Methods Blood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE. Results French children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets. Conclusions Our study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.

CITATION EXPORT

Karine Adel-Patient, Florence Campeotto, Marta Grauso et al.. Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches. Frontiers in Immunology. (2023). https://doi.org/10.3389/fimmu.2023.1108895

AUTHORS

15 · 8 CENTRES

Karine Adel-Patient, Florence Campeotto, Marta Grauso, Blanche Guillon, Marco Moroldo, Eric Venot, Céline Dietrich, François Machavoine, Florence A. Castelli, François Fenaille, Thierry Jo Molina, Patrick Barbet, Christophe Delacourt, Maria Leite-de-Moraes, Guillaume Lezmi

1 Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), Gif-sur-Yvette, France
2 AP-HP, Hôpital Necker-Enfants Malades, Service de Gastro-Entérologie et Nutrition Pédiatriques, Paris, France
3 Université de Paris Cité, INSERM UMR1139, Laboratoire de Microbiologie, Faculté de Pharmacie, Paris, France
4 Université Paris Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, France
5 Université Paris Cité, CNRS UMR 8253, Inserm UMR 1151, Institut Necker Enfants Malades, Equipe Immunorégulation et Immunopathologie, Paris, France
6 Université de Paris, UMRS 1138, INSERM, Sorbonne Paris-Cité, Paris, France
7 AP-HP, Centre-Université de Paris, hôpital Necker-Enfant-Malades, Service d'Anatomie et Cytologie Pathologiques, Paris, France
8 AP-HP, Hôpital Necker-Enfants Malades, Service de Pneumologie et Allergologie Pédiatriques, Paris, France