Noninvasive Biomarkers Correlated With Esophageal Eosinophilic Infiltrate in Pediatric Patients With Eosinophilic Esophagitis

Eosinophilic esophagitis is a recent and emerging chronic disease, secondary to eosinophilic infiltration of the esophageal mucosa leading to esophageal dysfunction. The diagnosis of this pathology, and monitoring of the efficacy of therapies, relies on the assessment of eosinophilic density on esophageal biopsies: follow-up requires numerous digestive endoscopies under general anesthesia, at each therapeutic change, to assess remission. The search for non-invasive biomarkers of active eosinophilic esophagitis is therefore a subject of major interest.

The first step is to study EDN (Eosinophil-Derived Neurotoxin), a protein secreted when eosinophils are activated. Several studies have investigated the association between serum EDN, EDN on esophageal brushing or esophageal biopsies with eosinophilic esophagitis activity, and the results look promising. Urinary EDN is associated with atopy but has not been studied in eosinophilic esophagitis. EDN is a biomarker of interest because it is stable over time and, above all, can be measured routinely, making it applicable to routine patient management and care. Our main objective is to evaluate the correlation of EDN in urine, blood and esophageal brushings with the eosinophilic infiltrate counted on esophageal biopsies in patients undergoing upper GI endoscopy at Trousseau Hospital for suspected eosinophilic esophagitis, or as part of the re-evaluation of known eosinophilic esophagitis under treatment.

Finally, esophageal and salivary dysbiosis has been described in eosinophilic esophagitis without direct evidence of its influence on esophageal inflammation and disease. Our secondary objective is to study the esophageal, salivary and fecal microbiota in these same patients in order to describe the composition, alpha and beta-diversity of bacterial and mycological flora between patients and controls, as well as their association with pathology, and to propose possible alternative therapies aimed at modulating the esophageal and/or salivary microbiota in the management of eosinophilic esophagitis.

This study will be carried out on a cohort of pediatric patients followed up in the pediatric nutrition and gastroenterology department of the Trousseau-APHP hospital and hospitalized for upper GI endoscopy, either as part of a suspected case of eosinophilic esophagitis, or during follow-up of a previously known case of eosinophilic esophagitis. Blood, urine, stool, saliva, 4 additional esophageal biopsies and esophageal brushings were collected on the day of the digestive endoscopy. Depending on the eosinophilic densitý on the biopsies, subjects will be classified into either the "patient with active eosinophilic esophagitis" group, the "patient with eosinophilic esophagitis in remission" group, or the "control without eosinophilic esophagitis" group. The investigator aim to include 60 patients undergoing upper GI endoscopy, at least half of whoḿ will have active or remitting eosinophilic esophagitis.

Furthermore, the study of the immunological, allergological and metabolomic signature of this disease is essential to enable the identification of new biomarkers to guide the creation of models combining several biomarkers predictive of eosinophilic density on esophageal biopsies. In a second step, the concentration of a panel of cytokines in blood and esophageal biopsies, the allergic sensitization profile in blood and esophageal biopsies, and an untargeted description of esophageal metabolomics will be compared between groups. In terms of clinical prospects, the investigator plan to develop a patient follow-up strategy based on the biomarkers studied, which is better adapted to clinical practice, better tolerated by patients and less costly than repeated endoscopies with esophageal biopsies.