title: Altered Esophageal Mucosal Structure in Patients with Celiac Disease.
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.
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: María Inés
authors.initials: MI
authors.lastname: Pinto-Sánchez
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina; Favaloro University Hospital, 1093 Buenos Aires, Argentina.
authors.forename: Fabio D
authors.initials: FD
authors.lastname: Nachman
authors.affiliation: Favaloro University Hospital, 1093 Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fuxman
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: Guido
authors.initials: G
authors.lastname: Iantorno
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: Hui Jer
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Favaloro University Hospital, 1093 Buenos Aires, Argentina.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ditaranto
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Costa
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Longarini
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: Xuan Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: Xianxi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina; Consejo de Investigación en Salud, MSAL, Gobierno de la Ciudad Autónoma de Buenos Aires, 1425 Buenos Aires, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Vázquez
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: María L
authors.initials: ML
authors.lastname: Moreno
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina; Consejo de Investigación en Salud, MSAL, Gobierno de la Ciudad Autónoma de Buenos Aires, 1425 Buenos Aires, Argentina.
authors.forename: Sonia
authors.initials: S
authors.lastname: Niveloni
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: Premysl
authors.initials: P
authors.lastname: Bercik
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina; Consejo de Investigación en Salud, MSAL, Gobierno de la Ciudad Autónoma de Buenos Aires, 1425 Buenos Aires, Argentina.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Smecuol
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mazure
authors.affiliation: Favaloro University Hospital, 1093 Buenos Aires, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bilder
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina.
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Mauriño
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
authors.affiliation: Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital, 1264 Buenos Aires, Argentina; Consejo de Investigación en Salud, MSAL, Gobierno de la Ciudad Autónoma de Buenos Aires, 1425 Buenos Aires, Argentina; Gastroenterology Chair, Universidad del Salvador, 1056 Buenos Aires, Argentina.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Bai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002446:Celiac Disease / Q000150:complications* / Q000178:diet therapy / Q000473:pathology*; D062465:Claudin-3 / Q000235:genetics; D057167:Claudins / Q000235:genetics; D050782:Esophageal pH Monitoring; D004947:Esophagus / Q000473:pathology* / Q000503:physiopathology; D005110:Extracellular Space; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000150:complications*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology*; D011503:Transglutaminases / Q000378:metabolism; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000235:genetics
chemical_list: C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; D062465:Claudin-3; D057167:Claudins; D012333:RNA, Messenger; D062826:Zonula Occludens-1 Protein; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins