The only way to know whether a patient with eosinophilic esophagitis (EoE) will respond to proton pump inhibitors (PPI) is through a medication trial and follow-up biopsies. For PPI nonresponders, that approach delays achieving disease remission and increases the risk of complications.
Researchers at Brigham and Women’s Hospital hypothesized that differences in mucosal gene transcript expression might explain the differences in PPI treatment response. Instead, they found the transcriptional profiles in patients with PPI-responsive and -nonresponsive EoE are remarkably similar.
Matthew J. Hamilton, MD, a gastroenterologist in the Division of Gastroenterology, Hepatology and Endoscopy, Mayssan Muftah, MD, a research fellow in the Division, Walter W. Chan, MD, MPH, director of the Center for Esophageal/Motility Disorders, Amitabh Srivastava, MD, formerly at the Department of Pathology, and colleagues report their findings in Clinical and Translational Gastroenterology.
EoE was defined in this study as ≥15 eosinophils per high-powered field (hpf) on esophageal mucosal biopsies from initial diagnostic endoscopy in patients with symptoms of esophageal dysfunction. Patients were considered responders to an eight-week trial of twice-daily PPI if follow-up biopsy showed <15 eosinophils/hpf.
From an EoE database at the Brigham, the team identified 16 patients with PPI-responsive EoE and 15 patients with PPI-nonresponsive EoE. Those groups had no significant differences in demographics, symptoms, or endoscopic findings.
For the two patient groups and six control subjects, the researchers determined RNA transcript expression in mid-esophagus biopsies using a customized panel of 114 genes implicated in EoE pathogenesis. They noted the top upregulated and downregulated genes with at least a two-fold difference in expression that was statistically significant (P<0.05).
Esophageal mucosal transcript expression was similar between PPI-responsive EoE and PPI-nonresponsive EoE:
- 17 of the top 20 upregulated genes were shared when PPI-responsive patients were compared with controls, and PPI-nonresponsive patients were compared with controls
- All five of the top five downregulated genes were shared
Likewise, there were no significant differences when transcript expression was directly compared in PPI-responsive and PPI-nonresponsive EoE.
Toward Clinical Translation
These findings provide more molecular evidence that PPI-responsive EoE is a subset of EoE rather than a distinct entity such as reflux esophagitis. It may be possible to determine molecular markers that predict response to PPI before therapy is initiated. If so, there is also the potential to tailor therapy and identify novel therapeutic targets.