Abstract and Introduction
Abstract
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.
Introduction
The current diagnostic algorithm for eosinophilic esophagitis (EoE) requires upper endoscopy and biopsy, an invasive procedure, to assess for esophageal eosinophilia in patients with symptoms of esophageal dysfunction. In practice, several procedures are needed: the index endoscopy where the diagnosis is suspected, the follow-up endoscopy to confirm the diagnosis after a proton pump inhibitor (PPI) trial, and a third endoscopy to assess tissue response to therapy. This approach is suboptimal because of high costs associated with the multiple procedures, as well as the possibility of procedural complications. Noninvasive biomarkers hold the potential to decrease costs and increase safety, but none has been clinically validated for routine use in EoE.
Candidate biomarkers could be selected from the pathogenesis of EoE, which is currently thought to involve a Th2-mediated response to allergens. A number of cytokines, including interleukin (IL)-4, IL-5, and IL-13, chemokines, such as eotaxin-3, which is the most highly upregulated gene in EoE, and markers of eosinophil activation, such as granule proteins, have all been shown to be elevated in EoE as compared with controls. However, these findings have been generally reported in the esophageal tissue, and data are primarily related to pathogenic studies in EoE. The true clinical utility of Th2-related cytokines, chemokines, and eosinophil granules as noninvasive serum biomarkers has yet to be demonstrated for either diagnosis or monitoring of treatment for EoE. Given the high cost of diagnosis and management of EoE using endoscopy findings, the translation of the research findings above into a viable serum test for the presence and/or severity of EoE would be of enormous value.
The aim of this study was to determine whether a panel of serum biomarkers based on the known pathogenesis of EoE could distinguish EoE from controls at baseline for diagnosis of EoE. We additionally sought to determine whether these biomarkers might have utility for monitoring EoE after treatment. We hypothesized that subjects with EoE would have significantly higher serum levels of one or more of these biomarkers, compared with clinically relevant non-EoE controls, and that these levels might decrease among the EoE cases after effective steroid therapy.