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

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.

Worse clinical course of disease in Crohn's patients with previous appendectomy.

OBJECTIVES: The aim of the present study was to assess the effect of previous appendectomy in a series of Crohn's disease (CD) patients on the clinical characteristics and course of disease. METHODS: Demographic and clinical data were retrospectively analysed for 129 consecutive outpatients (68 men and 61 women, median age 38 years) with CD. For each patient, information concerning appendectomy, indication for surgery (acute/chronic) and the date of surgery were recorded. The date of the appendectomy in relation to the date of CD diagnosis was carefully assessed in order to evaluate the precise relationship between the two events. A total of 129 CD patients who had not undergone previous appendectomy served as controls. The severity of disease was assessed retrospectively by evaluating the need for systemic steroids, immunosuppressants and surgical treatment for CD, particularly resective procedures. RESULTS: Forty-one CD patients (31.8%) underwent appendectomy before the diagnosis of disease. Appendectomy before diagnosis showed a negative association with colonic disease localization and with articular manifestations. In addition, the 41 patients with previous appendectomy had a significantly greater risk of surgery, particularly resective. Multivariate analysis confirmed appendectomy performed before diagnosis as an independent risk factor for surgery; on the contrary, colonic site and inflammatory type of disease were independent factors protecting against surgery. Although current smokers were at an increased risk of surgical treatment, a smoking habit alone did not seem to be relevant at the multivariate analysis. CONCLUSION: The results of this study indicate a worse clinical course of CD in patients appendicectomized before diagnosis.