Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study

Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical–pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states. We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis. The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p