title: Impaired epithelial integrity in the duodenal mucosa in early stages of celiac disease.
abstract: The small-bowel mucosal damage characteristic of celiac disease (CD) develops from normal villus morphology to inflammation and finally to villus atrophy with crypt hyperplasia. Patients with early stage CD may already suffer from abdominal symptoms before the development of villus atrophy. Although epithelial junctional integrity is compromised in overt disease, the appearance of such changes in early phases of the disorder is not known. We investigated whether alterations in epithelial junction protein expression occur already in early stage CD with normal mucosal morphology, and whether this correlates with inflammation indicators and clinical symptoms. The study involved 10 patients with early stage and 10 patients with overt villus atrophy that were followed yearly according to the study protocol. As controls, 20 nonceliac subjects were included. The expression of junction proteins (occludin, claudin 3, zonula occludens 1, and E-cadherin) was studied in small-intestinal biopsies using immunohistochemistry and Western blot. The correlation between junctional proteins and mucosal morphology, autoantibodies, the number of intraepithelial lymphocytes (IELs), and gastrointestinal symptoms was assessed. The expression of all junction proteins was already decreased in early stage CD when compared with nonceliac controls (P < 0.05). Junction protein expression correlated positively with mucosal villus morphology and negatively with the number of IELs, the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score (R = -0.314, P = 0.04). These findings show that the mucosal epithelial integrity is disrupted already in early stage CD before the disorder progresses to full-blown enteropathy.
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Rauhavirta
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland. Electronic address: katri.lindfors@uta.fi.
authors.forename: Katri
authors.initials: K
authors.lastname: Lindfors
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Koskinen
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Kaija
authors.initials: K
authors.lastname: Laurila
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Kalle
authors.initials: K
authors.lastname: Kurppa
authors.affiliation: Research Program Unit, Immunology, and Haartman Institute, Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Saavalainen
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Mäki
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Collin
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; Department of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Kaukinen
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D002446:Celiac Disease / Q000378:metabolism / Q000473:pathology*; D017630:Connexins / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D017630:Connexins