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

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.

Figure 1

Comparison of serum biomarkers for cases of EoE (black bars) and non-EoE controls (gray bars). The top of the bars represent the mean biomarker values, and the error bars represent the standard deviation. The y axis is on a log scale, and all concentrations are in pg/mL with the exception of major basic protein (MBP) which is in ng/mL.

Figure 2

(A) Comparison of serum biomarkers for cases of EoE before (black bars) and after (white bars) treatment with a topical corticosteroid. (B) Comparison for cases of EoE stratified by treatment response with pre-treatment (black bars), post-treatment responders at the <15 eos/hpf level (white bars), and non-responders at the ≥15 eos/hpf level (gray bars). For both panels, the top of the bars represent the mean biomarker values, the error bars represent the standard deviation, the y axis is on a log scale, and all concentrations are in pg/mL with the exception of major basic protein (MBP) which is in ng/mL.

Figure 2

(A) Comparison of serum biomarkers for cases of EoE before (black bars) and after (white bars) treatment with a topical corticosteroid. (B) Comparison for cases of EoE stratified by treatment response with pre-treatment (black bars), post-treatment responders at the <15 eos/hpf level (white bars), and non-responders at the ≥15 eos/hpf level (gray bars). For both panels, the top of the bars represent the mean biomarker values, the error bars represent the standard deviation, the y axis is on a log scale, and all concentrations are in pg/mL with the exception of major basic protein (MBP) which is in ng/mL.