RNA sequencing confirms similarities between PPI-responsive oesophageal eosinophilia and eosinophilic oesophagitis

Aliment Pharmacol Ther. 2018 Jul;48(2):219-225. doi: 10.1111/apt.14825. Epub 2018 Jun 4.

Abstract

Background: Although current American guidelines distinguish proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) from eosinophilic oesophagitis (EoE), these entities are broadly similar. While two microarray studies showed that they have similar transcriptomes, more extensive RNA sequencing studies have not been done previously.

Aim: To determine whether RNA sequencing identifies genetic markers distinguishing PPI-REE from EoE.

Methods: We retrospectively examined 13 PPI-REE and 14 EoE biopsies, matched for tissue eosinophil content, and 14 normal controls. Patients and controls were not PPI-treated at the time of biopsy. We did RNA sequencing on formalin-fixed, paraffin-embedded tissue, with differential expression confirmation by quantitative polymerase chain reaction (PCR). We validated the use of formalin-fixed, paraffin-embedded vs RNAlater-preserved tissue, and compared our formalin-fixed, paraffin-embedded EoE results to a prior EoE study.

Results: By RNA sequencing, no genes were differentially expressed between the EoE and PPI-REE groups at the false discovery rate (FDR) ≤0.01 level. Compared to normal controls, 1996 genes were differentially expressed in the PPI-REE group and 1306 genes in the EoE group. By less stringent criteria, only MAPK8IP2 was differentially expressed between PPI-REE and EoE (FDR = 0.029, 2.2-fold less in EoE than in PPI-REE), with similar results by PCR. KCNJ2, which was differentially expressed in a prior study, was similar in the EoE and PPI-REE groups by both RNA sequencing and real-time PCR.

Conclusion: Eosinophilic oesophagitis and PPI-REE have comparable transcriptomes, confirming that they are part of the same disease continuum.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Case-Control Studies
  • Eosinophilia / complications
  • Eosinophilia / drug therapy*
  • Eosinophilia / genetics*
  • Eosinophilia / pathology
  • Eosinophilic Esophagitis / genetics*
  • Eosinophilic Esophagitis / pathology
  • Esophagitis, Peptic / complications
  • Esophagitis, Peptic / drug therapy*
  • Esophagitis, Peptic / genetics*
  • Esophagitis, Peptic / pathology
  • Female
  • Gastroesophageal Reflux / drug therapy
  • Gastroesophageal Reflux / etiology
  • Gastroesophageal Reflux / genetics
  • Gastroesophageal Reflux / pathology
  • Humans
  • Male
  • Microarray Analysis
  • Middle Aged
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Sequence Analysis, RNA
  • Transcriptome
  • Treatment Outcome
  • Young Adult

Substances

  • Proton Pump Inhibitors