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.