Leana L. Higgins

Utility of a Noninvasive Serum Biomarker Panel for Diagnosis and Monitoring of Eosinophilic Esophagitis: A Prospective Study.

OBJECTIVES:Noninvasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE.METHODS:We conducted a prospective cohort study of consecutive adults undergoing outpatient esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded manner for interleukin (IL)-4, IL-5, IL-6, IL-9, IL-13, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor-α, eotaxin-1, -2, and -3, thymic stromal lymphopoietin (TSLP), major basic protein, and eosinophil-derived neurotoxin. Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases.RESULTS:A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85±160 vs. 43±161 pg/ml (P=0.12) and 41±159 vs. 21±73 (P=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response.CONCLUSIONS:A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed.

A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study

OBJECTIVES:Eosinophilic esophagitis (EoE) is difficult to distinguish from gastroesophageal reflux (GERD) and other causes of dysphagia. We assessed the utility of a set of clinical and endoscopic features for predicting EoE without obtaining esophageal biopsies.METHODS:We prospectively enrolled consecutive adults undergoing outpatient upper endoscopy at the University of North Carolina from July 2011 through December 2013. Incident cases of EoE were diagnosed per consensus guidelines. Non-EoE controls had either GERD- or dysphagia-predominant symptoms. A predictive model containing clinical and endoscopic, but no histological, data was assessed. Receiver operator characteristic curves were constructed and the area under the curve (AUC) was calculated.RESULTS:A total of 81 EoE cases (mean age 38 years; 60% male; 93% white; 141 eosinophils per high-power field (eos/hpf)) and 144 controls (mean age 52, 38% male; 82% white; 3 eos/hpf) were enrolled. A combination of clinical (age, sex, dysphagia, food allergy) and endoscopic (rings, furrows, plaques, hiatal hernia) features was highly predictive of EoE. The AUC was 0.944, with sensitivity, specificity, and accuracy of 84, 97, and 92%. Similar values were seen after limiting controls to those with only reflux or dysphagia or to those with esophageal eosinophilia not due to EoE.CONCLUSIONS:We validated a set of clinical and endoscopic features to predict EoE with a high degree of accuracy and allow identification of those at very low risk of disease. Use of these predictors at the point-of-care will avoid the effort and expense of low-yield histological examinations for EoE.

A Gene Expression Panel is Accurate for Diagnosis and Monitoring Treatment of Eosinophilic Esophagitis in Adults

OBJECTIVE: Eosinophilic esophagitis (EoE) can be difficult to diagnose. We aimed to evaluate whether a gene expression score could differentiate adult EoE cases from non‐EoE controls and to determine whether scores normalized after treatment for EoE. METHODS: We analyzed prospectively collected esophageal biopsies from EoE patients (diagnosed as per consensus guidelines and after a proton pump inhibitor trial) and non‐EoE controls. Gene expression for a previously constructed 94 gene panel was quantified for a single RNA‐later preserved biopsy. For diagnosis, a summary expression score and the area under the receiver operating characteristic curve (AUC) were calculated. For treatment response (defined as <15 eosinophils per high‐power field), pretreatment and posttreatment EoE samples were compared. RESULTS: For 91 EoE cases and 174 controls, gene scores for EoE cases were lower than non‐EoE controls (mean 198 vs. 420; P<0.001), with an AUC of 0.927. A score ≤263 yielded a positive predictive value=91%; a score ≥349 yielded a negative predictive value=90%; only 12% of subjects had an indeterminate score (264–348) by this classification scheme. For the 89 EoE cases with paired pretreatment and posttreatment samples, overall gene scores improved after treatment from 199 to 343 (P<0.001). This normalization was seen only in cases with histological response (202 vs. 425; P<0.001); scores were unchanged in non‐responders (189 vs. 226; P=0.25). CONCLUSIONS: A gene expression score has high diagnostic utility for distinguishing EoE patients from non‐EoE controls in adults and can be used in clinical algorithms. Because it is highly responsive to treatment, the test could be used to monitor disease status.

Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis

Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non‐invasive biomarker.

Su1112 A Set of Clinical and Endoscopic Features Predicts the Presence of Eosinophilic Esophagitis With High Accuracy, Allowing Omission of Low-Yield Biopsies: Results From a Prospective Study

increasing in the population especially in pediatrics and reach 1:1000 in diseases such as EoE (Eosinophilic Esophagitis) (Lee 2013). CD24 is a small, mucin-like glycoprotein that functions both in signal transduction and as an adhesion molecule (Sagiv, 2008). CD24 is expressed on many hematopoietic cells, non-hematopoietic cells and malignancies (Fang, 2010). Previous studies in eosinophils have suggested CD24 as an IL-5-upregulated gene that is involved in eosinophil apoptosis and survival (Temple, 2011). The role evoked for CD24 in IL-5-induced survival of eosinophils remains to be investigated. We hypothesize that CD24 is a key molecular checkpoint, regulating eosinophil functions in chronic mucosal GI diseases, all of which are characterized by significant eosinophil infiltration. Aim: 1) To assess the expression of CD24 in eosinophils in the GI tract in wild-type (WT) mice; 2) To assess the level of eosinophils in the GI tract in CD24 knockout (-/-) and to compare it to WT mice.Methods: We have previously established a colony of CD24-/mice, on a C57BL/ 6J genetic background, and their WT littermates at our local animal facility. The levels of eosinophils were assessed in WT and CD24-/mice. Bone marrow (BM) cells were collected, and grown in medium containing 10 ng/mL recombinant mouse interleukin-5 (rmIL-5). On day 13 the cells were counted and levels of eosinophils were assessed by FACS. The levels of eosinophil and CD24 expression in different tissues were also evaluated. Results: Eosinophil counts in BM extracted from mice were significantly (p-value=0.0436) higher in CD24-/compared to WT mice, (Fig. 1). Fluorescense intensity was stronger in CD24-/compared to WT mice even though there were no differences in the eosinophil population of mature cells (Fig 2). Eosinophil count was higher in BM from CD24-/compared to WT mice, and lower in blood and addipose tissue (Fig. 3). CD24 expression was higher in peripheral tissues compared to the blood and BM (Fig 4). Conclusion: Based on our preliminary results, it is suggested that CD24 has an important role in negatively regulating eosinophil proliferation/maturation/chemotaxis. Understanding the role of eosinophil in GI disorders may have a large imapct on our understanding of the EGIDs. Targeting specific proteins that play an important role in these processes may lead to novel therapeutic approaches

Su1113 In Search of a Non-Invasive Blood Test for Diagnosis and Monitoring of EoE: A Prospective Study of a Serum Biomarker Panel

increasing in the population especially in pediatrics and reach 1:1000 in diseases such as EoE (Eosinophilic Esophagitis) (Lee 2013). CD24 is a small, mucin-like glycoprotein that functions both in signal transduction and as an adhesion molecule (Sagiv, 2008). CD24 is expressed on many hematopoietic cells, non-hematopoietic cells and malignancies (Fang, 2010). Previous studies in eosinophils have suggested CD24 as an IL-5-upregulated gene that is involved in eosinophil apoptosis and survival (Temple, 2011). The role evoked for CD24 in IL-5-induced survival of eosinophils remains to be investigated. We hypothesize that CD24 is a key molecular checkpoint, regulating eosinophil functions in chronic mucosal GI diseases, all of which are characterized by significant eosinophil infiltration. Aim: 1) To assess the expression of CD24 in eosinophils in the GI tract in wild-type (WT) mice; 2) To assess the level of eosinophils in the GI tract in CD24 knockout (-/-) and to compare it to WT mice.Methods: We have previously established a colony of CD24-/mice, on a C57BL/ 6J genetic background, and their WT littermates at our local animal facility. The levels of eosinophils were assessed in WT and CD24-/mice. Bone marrow (BM) cells were collected, and grown in medium containing 10 ng/mL recombinant mouse interleukin-5 (rmIL-5). On day 13 the cells were counted and levels of eosinophils were assessed by FACS. The levels of eosinophil and CD24 expression in different tissues were also evaluated. Results: Eosinophil counts in BM extracted from mice were significantly (p-value=0.0436) higher in CD24-/compared to WT mice, (Fig. 1). Fluorescense intensity was stronger in CD24-/compared to WT mice even though there were no differences in the eosinophil population of mature cells (Fig 2). Eosinophil count was higher in BM from CD24-/compared to WT mice, and lower in blood and addipose tissue (Fig. 3). CD24 expression was higher in peripheral tissues compared to the blood and BM (Fig 4). Conclusion: Based on our preliminary results, it is suggested that CD24 has an important role in negatively regulating eosinophil proliferation/maturation/chemotaxis. Understanding the role of eosinophil in GI disorders may have a large imapct on our understanding of the EGIDs. Targeting specific proteins that play an important role in these processes may lead to novel therapeutic approaches

Tu1130 Impact of Clinical and Endoscopic Features on BMI in Patients With Eosinophilic Esophagitis

G A A b st ra ct s standard grocery store for the SFED needed more items from a second store to complete his/her shopping when compared to a patient consuming an unrestricted diet (39% vs 4%; p=0.008; Table 2). The prices of the SFED and unrestricted diet just using a specialty supermarket were comparable (

Accuracy of the Eosinophilic Esophagitis Endoscopic Reference Score in Diagnosis and Determining Response to Treatment

104.86 vs 108.25; p=0.84), as was the percentage of items requiring a trip to a second store (5% vs 1%; p=0.25). Shopping at a specialty grocery store increased weekly grocery costs by

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis

27.93 (p=0.008) for the SFED and

Mo1210 Utility of Serum Periostin for Diagnosis and Monitoring of Eosinophilic Esophagitis: Results From a Prospective Study

42.31 (p=0.008) for the unrestricted diet. Conclusions: For a patient shopping at a standard grocery store, the cost of an SFED is higher than the cost of an unrestricted diet (~