Biette, Kathryn A.

OBJECTIVES: Eosinophilic esophagitis (EoE), a chronic food allergic disease, lacks sensitive and specific peripheral biomarkers. We hypothesized that levels of EoE-related biomarkers captured using a 1-hour minimally invasive Esophageal String Test (EST) would correlate with mucosal eosinophil counts and tissue concentrations of these same biomarkers. We aimed to determine whether a 1-hour EST accurately distinguishes active from inactive EoE or a normal esophagus. METHODS: In a prospective, multisite study, children and adults (ages 7–55 years) undergoing a clinically indicated esophagogastroduodenoscopy performed an EST with an esophageal dwell time of 1 hour. Subjects were divided into 3 groups: active EoE, inactive EoE, and normal esophageal mucosa. Eosinophil-associated protein levels were compared between EST effluents and esophageal biopsy extracts. Statistical modeling was performed to select biomarkers that best correlated with and predicted eosinophilic inflammation. RESULTS: One hundred thirty-four subjects (74 children, 60 adults) with active EoE (n = 62), inactive EoE (n = 37), and patient controls with a normal esophagus (n = 35) completed the study. EST-captured eosinophil-associated biomarkers correlated significantly with peak eosinophils/high-power field, endoscopic visual scoring, and the same proteins extracted from mucosal biopsies. Statistical modeling, using combined eotaxin-3 and major basic protein-1 concentrations, led to the development of EoE scores that distinguished subjects with active EoE from inactive EoE or normal esophagi. Eighty-seven percent of children, 95% of parents, and 92% of adults preferred the EST over endoscopy if it provided similar information. DISCUSSION: The 1-hour EST accurately distinguishes active from inactive EoE in children and adults and may facilitate monitoring of disease activity in a safe and minimally invasive fashion.

AbstractBackgroundEosinophilic esophagitis (EoE) is a chronic antigen‐mediated clinicopathologic disease of the esophagus characterized by an eosinophil‐predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte‐macrophage colony‐stimulating factor (GM‐CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE.MethodsEosinophilic esophagitis‐like esophageal inflammation was induced in the L2‐IL5OXA EoE mouse model, and GM‐CSF production was assessed by mRNA and protein analyses. Granulocyte‐macrophage colony‐stimulating factor‐receptor‐alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2‐IL5OXA EoE mice were treated with anti‐GM‐CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT‐PCR.ResultsSignificantly increased levels of esophageal GM‐CSF expression was detected in the L2‐IL5OXA mouse EoE model during active inflammation. Granulocyte‐macrophage colony‐stimulating factor‐receptor‐alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti‐GM‐CSF neutralization in L2‐IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation.ConclusionGranulocyte‐macrophage colony‐stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.