Wheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms in response to wheat ingestion, without the characteristic serological or histological evidence of coeliac disease. The aetiology and mechanism of these symptoms are unknown, and no biomarkers have been identified. We aimed to determine if sensitivity to wheat in the absence of coeliac disease is associated with systemic immune activation that may be linked to an enteropathy.
Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage.
Coeliac disease (CD) incidence has increased in recent decades, characterised by variations according to sex, age at diagnosis, year of birth, month of birth and region of birth. Genetic susceptibility and exposure to gluten are the necessary factors in CD aetiology, although several environmental factors are considered.
Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.
There is debate over the existence of nonceliac gluten sensitivity (NCGS) intestinal and extraintestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS.
The first electrochemical immunosensor (EI) for the detection of antibodies against deamidated gliadin peptides (DGP) is described here. A disposable nanohybrid screen-printed carbon electrode modified with DGP was employed as the transducer’s sensing surface. Real serum samples were successfully assayed and the results were corroborated with an ELISA kit. The presented EI is a promising analytical tool for celiac disease diagnosis.
Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy and production of several autoantibodies of which endomysial, tissue transglutaminase and deamidated gliadin peptide antibodies are considered specific. Although anti-reticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This review highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.
Gluten intolerance is an umbrella term for gluten-related disorders manifested in health decline as a result of the gluten ingestion. The spectrum of gluten-related disorders includes three major groups: autoimmune (mainly, Celiac Disease, CD, also known as Celiac Sprue, dermatitis herpetiformis, or gluten-sensitive ataxia), allergic (wheat allergy, WA), and non-autoimmune non-allergic (non-celiac gluten sensitivity, NCGS, or gluten sensitivity, GS). Pathogenesis and diagnostics of CD and WA are well established in contrast to NCGS, pathogenicity of which is still poorly understood and its symptoms are frequently misdiagnosed since most of the NCGS cases are currently identified via the process of CD and WA exclusion. By now, the only one proven effective way for CD treatment is gluten-free diet (GFD). However, such an increasingly gaining popularity diet is apparently unsuitable for NCGS treatment because in this case gluten does not always arise as the major or exclusive culprit of gastrointestinal disorder. Furthermore, it is some physicians' opinion that GFD can be deficient in fiber and in other vitamins and minerals. In many cases, GFD is commercially inaccessible for the most needy, whereas strict adherence to the diet is complicated by the presence of small amounts of the gluten components in some foods and even medicines. In this regard, a number of research groups and pharmaceutical companies are extensively developing alternative medicinal approaches to GFD for effective gluten intolerance treatment. This review summarizes our understanding of gluten-related disorders, possible mechanisms of gluten intolerance activation and advantages of gluten intolerance medicinal treatment using novel drug candidates obtained with a proper pharmaceutical design.
Until recently gluten intolerance has been believed to be typical of celiac disease (CD) and wheat allergy (WA). In the last few years, however, several study results have been published that have proved that gluten intolerance can also affect people who do not suffer from any of the above mentioned diseases. The new syndrome has been named non-celiac gluten sensitivity (NCGS) or gluten sensitivity (GS). It has been included in the new list of gluten-related disorders published in 2012. Researchers believe that NCGS is the most common syndrome of gluten intolerance. This review discusses many aspects of NCGS epidemiology, pathophysiology, clinical spectrum, and treatment and current tools to identify patients suffering from CD, WA, and NCGS.