Altered Esophageal Mucosal Structure in Patients with Celiac Disease

Can J Gastroenterol Hepatol. 2016:2016:1980686. doi: 10.1155/2016/1980686. Epub 2016 Feb 29.

Abstract

Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Celiac Disease / complications*
  • Celiac Disease / diet therapy
  • Celiac Disease / pathology*
  • Claudin-3 / genetics
  • Claudins / genetics
  • Esophageal pH Monitoring
  • Esophagus / pathology*
  • Esophagus / physiopathology
  • Extracellular Space
  • Female
  • GTP-Binding Proteins / metabolism
  • Gastroesophageal Reflux / complications*
  • Gene Expression
  • Humans
  • Male
  • Manometry
  • Middle Aged
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology*
  • Protein Glutamine gamma Glutamyltransferase 2
  • RNA, Messenger / metabolism
  • Tight Junctions / metabolism
  • Tight Junctions / pathology*
  • Transglutaminases / metabolism
  • Young Adult
  • Zonula Occludens-1 Protein / genetics

Substances

  • CLDN2 protein, human
  • CLDN3 protein, human
  • Claudin-3
  • Claudins
  • RNA, Messenger
  • Zonula Occludens-1 Protein
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins