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Dietary Factors and Mucosal Immune Response in Celiac Disease Patients Having Persistent Symptoms Despite a Gluten-free Diet

Laurikka, Pilvi MD*,†; Lindfors, Katri PhD*; Oittinen, Mikko MSc; Huhtala, Heini MSc§; Salmi, Teea MD, PhD; Lähdeaho, Marja-Leena MD, PhD; Ilus, Tuire MD, PhD; Mäki, Markku MD, PhD; Kaukinen, Katri MD, PhD*,#; Kurppa, Kalle MD, PhD

Journal of Clinical Gastroenterology: August 2019 - Volume 53 - Issue 7 - p 507–513
doi: 10.1097/MCG.0000000000001013
ALIMENTARY TRACT: Original Articles
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Goals: The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients.

Background: For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa.

Study: We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD. The density of CD3+ and γδ+ intraepithelial lymphocytes (IELs), CD25+ and FOXP3+ regulatory T cells, and CD117+ mast cells, and the expression of tight junction proteins claudin-3 and occludin, heat shock protein 60, interleukin 15, and Toll-like receptor 2 and 4 were evaluated in duodenal biopsies.

Results: All subjects kept a strict GFD and had negative celiac autoantibodies and recovered mucosal morphology. The asymptomatic patients had higher mean fiber intake (20.2 vs. 15.2 g/d, P=0.028) and density of CD3+ IELs (59.3 vs. 45.0 cell/mm, P=0.045) than those with persistent symptoms. There was a similar but nonsignificant trend in γδ+ IELs (17.9 vs. 13.5, P=0.149). There were no differences between the groups in other parameters measured.

Conclusions: Low fiber intake may predispose patients to persistent symptoms in celiac disease. There were no differences between the groups in the markers of innate immunity, epithelial stress or epithelial integrity. A higher number of IELs in asymptomatic subjects may indicate that the association between symptoms and mucosal inflammation is more complicated than previously thought.

*Celiac Disease Research Center, Faculty of Medicine and Life Sciences

§Faculty of Social Sciences

Departments of Dermatology

#Internal Medicine, Tampere University Hospital, Faculty of Medicine and Life Sciences, University of Tampere

Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital

Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere

Seinäjoki Central Hospital, Seinäjoki, Finland

Supported by the Academy of Finland, the Sigrid Juselius Foundation, the Päivikki and Sakari Sohlberg Foundation, the Competitive State Research Financing of the Expert Area of Tampere University Hospital, the Mary and Georg Ehrnrooth Foundation, the Foundation for Pediatric Research, the Yrjö Jahnsson Foundation, and the Hospital District of South Ostrobothnia.

The authors declare that they have nothing to disclose.

Address correspondence to: Kalle Kurppa, MD, PhD, Centre for Child Health Research, University of Tampere, Lääkärinkatu 1, Tampere 33014, Finland (e-mail: kalle.kurppa@uta.fi).

Received July 31, 2017

Accepted January 16, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.