Eosinophil-Derived Transcript Signatures in Oesophageal Biopsies and Peripheral Blood from Patients with Eosinophilic Oesophagitis: A Review

Abstract

Eosinophilic oesophagitis is diagnosed by counting eosinophils in a biopsy, which is a subjective measure of a patchy disease. Transcript profiling of the same tissue performs better than the count it is measured against. Blood, which would spare the endoscopy altogether, does not. Objectives: To review the published evidence on eosinophil-derived and epithelial transcript signatures in eosinophilic oesophagitis: what the oesophageal transcriptome contains, how a targeted molecular panel performs against histology, and how far peripheral blood markers track the tissue. Material and Methods: Narrative review of transcriptome and expression profiling studies, molecular panel validations, biomarker correlation cohorts, consensus criteria and histology scoring studies indexed in PubMed and the major gastroenterology and allergy journals. Studies were eligible if they reported the accuracy of a molecular or blood marker against oesophageal histology in a defined population, or the reproducibility of the histological reference itself. No new patient data were generated; every estimate quoted is one published by the original investigators. Results: Genome-wide profiling identified a transcript signature involving approximately one per cent of the human genome, conserved across sex, age
and allergic status and distinct from non-eosinophilic chronic oesophagitis, with the eosinophil chemoattractant eotaxin-3 the most highly induced transcript. A targeted 96-gene panel derived from that signature identified adult and paediatric patients with approximately 96 per cent sensitivity and 98 per cent specificity across 194 validation samples, retained 96 per cent sensitivity and 100 per cent specificity on archival formalin-fixed material, and distinguished disease in remission from controls. In peripheral blood, absolute eosinophil count, eosinophil-derived neurotoxin and eotaxin-3 correlated with oesophageal eosinophil density at r = 0.56, 0.54 and 0.32 respectively, while eotaxin-1, eotaxin-2, interleukin 5 and faecal neurotoxin did not correlate at all. Conclusion: The tissue transcriptome outperforms the eosinophil count that serves as its reference standard, and does so on the archival material most
laboratories already hold. Blood markers rise in active disease but correlate only moderately with tissue, which makes them plausible for monitoring a known patient and inadequate for diagnosis. Abbreviations: EoE – Eosinophilic Oesophagitis, EDP – EoE Diagnostic Panel, CCL26 – Chemokine (C-C Motif) Ligand 26 (Eotaxin-3), AEC – Absolute Eosinophil Count, EDN – Eosinophil-Derived Neurotoxin, eos/hpf – Eosinophils per High-Power Field, FFPE – Formalin-Fixed Paraffin-Embedded,qPCR – Quantitative Polymerase Chain Reaction, EoEHSS – EoE Histology Scoring System, PPI – Proton Pump Inhibitor, GORD – Gastro-Oesophageal Reflux Disease, IL – Interleukin.