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.
Highlights
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten
Clinical and laboratory characteristics of Glutensensitive individuals (GS) subjects The patients who fulfilled the GS diagnostic criteria experienced symptoms overlapping those presented by CD patients, but their symptoms resolved within a few days after the implementation of the gluten-free diet, and they remained symptom-free for the entire follow-up period
Intestinal permeability While CD is consistently associated with impaired mucosal barrier function and increased small intestinal permeability, it is not known whether patients with GS present similar alterations
Summary
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Glutensensitive 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. Besides CD and wheat allergy, there are cases of gluten reactions in which neither allergic nor autoimmune mechanisms are involved. These are generally defined as gluten sensitivity (GS) [2,3,4,5]. While the gastrointestinal symptoms in GS may resemble those associated with CD, the overall clinical picture is generally less severe and is not accompanied by the concurrence of tTG autoantibodies or autoimmune disease. The diagnosis is made by exclusion, and an elimination diet and “open challenge” (that is, the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether the patient’s health improves with the elimination or reduction of gluten from the diet
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