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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number23
JournalBMC Medicine
Volume9
DOIs
StatePublished - Mar 9 2011

ASJC Scopus subject areas

  • Medicine(all)

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