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

Abstract

BackgroundCeliac 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.MethodsCD, 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.ResultsUnlike 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).ConclusionsThis 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.

Psoriasis as an autoimmune disease

“…U pacjentów z łuszczycą obserwuje się najczęściej współistnienie łuszczycowego zapalenia stawów, reumatoidalnego zapalenia stawów (RZS), nieswoistych zapaleń jelit [3], stwardnienia rozsianego, autoimmunologicznych chorób tarczycy [4] oraz celiakii [5][6][7][8]. Silniejszy niż w łuszczycy zwykłej związek z chorobami autoimmunologicznymi występuje w przypadku łuszczycowego zapalenia stawów [9,10].…”

Nutritional status variation and intestinal and extra intestinal symptomatology in patients with celiac disease and non-celiac gluten sensitivity given specialized dietary advice

“…The present study and Sapone et al 29 found that the most reported symptoms by both groups involved the gastrointestinal tract, followed by symptomatology associated with energy/activity and emotions.…”

Editorial: Non-Celiac Wheat Sensitivity: Separating the Wheat from the Chat!

“…In an expanded data set ( n = 26 GS patients), the same investigators reported that GS was not associated with increased intestinal permeability (using lactulose / mannitol). Additional adaptive immunity markers (interleukin-6 and interleukin-21) were also less likely to be expressed in patients with GS while a marker of innate immunity the Toll-like receptor 2 was increased ( 43 ). A point of interest is that 4 of the 26 patients with GS had raised intraepithelial lymphocytes on duodenal biopsy.…”