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BMC Medicine
Published in: BMC Medicine 1/2011

Open Access 01-12-2011 | Research article

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

Authors: Anna Sapone, Karen M Lammers, Vincenzo Casolaro, Marcella Cammarota, Maria Teresa Giuliano, Mario De Rosa, Rosita Stefanile, Giuseppe Mazzarella, Carlo Tolone, Maria Itria Russo, Pasquale Esposito, Franca Ferraraccio, Maria Cartenì, Gabriele Riegler, Laura de Magistris, Alessio Fasano

Published in: BMC Medicine | Issue 1/2011

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Abstract

Background

Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.

Methods

CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.

Results

Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293).

Conclusions

This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.
Appendix
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Metadata
Title
Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity
Authors
Anna Sapone
Karen M Lammers
Vincenzo Casolaro
Marcella Cammarota
Maria Teresa Giuliano
Mario De Rosa
Rosita Stefanile
Giuseppe Mazzarella
Carlo Tolone
Maria Itria Russo
Pasquale Esposito
Franca Ferraraccio
Maria Cartenì
Gabriele Riegler
Laura de Magistris
Alessio Fasano
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2011
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-9-23

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