celiac disease and gluten sensitivity: Divergence of gut permeability and mucosal immune gene expression

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Divergence of gut permeability and mucosal immune gene expression in two

gluten-associated conditions: celiac disease and gluten sensitivity.

<http://www.ncbi.nlm.nih.gov/pubmed/21392369>

Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De M,

Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio

F, Carteni M, Riegler G, de Magistris L, Fasano A.

BMC Med. 2011 Mar 9;9(1):23.

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.