Results from the German registry for refractory celiac disease.

Refractory celiac disease (RCD) refers to a rare subgroup of patients with celiac disease who show clinical signs of malabsorption despite a gluten-free diet. RCD is divided into an autoimmune phenotype (RCD type I) and pre-lymphoma (RCD type II). To reflect the clinical reality in managing this disease in Germany, a national register was established based on a questionnaire developed specifically for this purpose. Between 2014 and 2020, a total of 53 patients were registered. The diagnosis of RCD was confirmed in 46 cases (87%). This included 27 patients (59%) with RCD type I and 19 patients (41%) with RCD type II. A wide range of diagnostic and therapeutic measures was used. Therapeutically, budesonide was used in 59% of the RCD patients regardless of the subtype. Nutritional therapy was used in only 5 patients (11%). Overall mortality was 26% (12 patients) with a clear dominance in patients with RCD type II (9 patients, 47%). In summary, RCD needs to become a focus of national guidelines to increase awareness, establish standards, and thus enable the treating physician to make the correct diagnosis in a timely manner. Moreover, we concluded that when treating such patients, contacting a specialized center is recommended to ensure sufficient management.

Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells.

Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from active and inactive CeD patients and healthy controls. PBMCs were sorted for expression of CD14 and co-cultured with intestinal epithelial cells (IECs, Caco2BBe). Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. Transepithelial resistance was found to be decreased only in IECs that had been exposed to celiac monocytes. In line with this, tight junctional alterations were found by confocal laser scanning microscopy and Western blotting of ZO-1, occludin, and claudin-5. Analysis of cytokine concentrations in monocyte supernatants revealed higher expression of interleukin-6 and MCP-1 in celiac monocytes. However, surface marker expression, as analyzed by FACS analysis after immunostaining, did not reveal significant alterations in celiac monocytes. In conclusion, CeD peripheral monocytes reveal an intrinsically elevated pro-inflammatory cytokine pattern that is associated with the potential of peripheral monocytes to affect barrier function by altering TJ composition.

Intestinal Barrier Function in Gluten-Related Disorders.

Gluten-related disorders include distinct disease entities, namely celiac disease, wheat-associated allergy and non-celiac gluten/wheat sensitivity. Despite having in common the contact of the gastrointestinal mucosa with components of wheat and other cereals as a causative factor, these clinical entities have distinct pathophysiological pathways. In celiac disease, a T-cell mediate immune reaction triggered by gluten ingestion is central in the pathogenesis of the enteropathy, while wheat allergy develops as a rapid immunoglobulin E- or non-immunoglobulin E-mediated immune response. In non-celiac wheat sensitivity, classical adaptive immune responses are not involved. Instead, recent research has revealed that an innate immune response to a yet-to-be-defined antigen, as well as the gut microbiota, are pivotal in the development in this disorder. Although impairment of the epithelial barrier has been described in all three clinical conditions, its role as a potential pathogenetic co-factor, specifically in celiac disease and non-celiac wheat sensitivity, is still a matter of investigation. This article gives a short overview of the mucosal barrier of the small intestine, summarizes the aspects of barrier dysfunction observed in all three gluten-related disorders and reviews literature data in favor of a primary involvement of the epithelial barrier in the development of celiac disease and non-celiac wheat sensitivity.

Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study.

BACKGROUND & AIMS: Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers. METHODS: We performed a prospective study of 1055 patients (888 adults; median age, 48 yrs and 167 children; median age, 10 yrs) referred to 8 endoscopy centers in Germany, for various indications, from January 2016 through June 2017. Patients were tested for celiac disease using Simtomax, which detects immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides (DGP). Results were compared with findings from histologic analyses of duodenal biopsies (reference standard). The primary aim was to determine the accuracy of this POCT for the detection of celiac disease, to identify candidates for duodenal biopsy. A secondary aim was to determine the prevalence of celiac disease in adult and pediatric populations referred for outpatient endoscopic evaluation. RESULTS: The overall prevalence of celiac disease was 4.1%. The POCT identified individuals with celiac disease with 79% sensitivity (95% CI, 64%-89%) and 94% specificity (95% CI, 93%-96%). Positive and negative predictive values were 37% and 99%. When we analyzed the adult and pediatric populations separately, we found the test to identify adults with celiac disease (prevalence 1.2%) with 100% sensitivity and 95% specificity. In the pediatric population (celiac disease prevalence 19.6%), the test produced false-negative results for 9 cases; the test therefore identified children with celiac disease with 72% sensitivity (95% CI 53%-86%). Analyses of serologic data revealed significantly lower DGP titers in the false-negative vs the true-positive group. CONCLUSIONS: In a study of more than 1000 adults and children, we found the Simtomax POCT to detect celiac disease with lower overall levels of sensitivity than expected. Although the test identifies adults with celiac disease with high levels of sensitivity and specificity, the prevalence of celiac disease was as low as 1.2% among adults. The test's lack of sensitivity might be due to the low intensity of the POCT bands and was associated with low serum DGP titers. Study ID no: DRKS00012499.

Gluten-Free Diet in Celiac Disease-Forever and for All?

The gluten-free diet is the only effective treatment available for celiac disease. However, it is difficult to adhere to and a closer look on the diet's implementation and indications reveals several ambiguities: Not only is there controversy on the threshold of gluten that can be tolerated in the frame of a strict gluten-free diet, but it is also unclear whether the gluten-free diet is an appropriate treatment in patient subgroups with asymptomatic or potential celiac disease. Reports from a number of research groups suggest that a certain proportion of patients may effectively develop tolerance to gluten and thus become suitable for gluten reintroduction over time. In this review, we set out to create an overview about the current state of research as regards the definition of a strict gluten-free diet in terms of the gluten thresholds considered tolerable and the indication for a gluten-free diet in the absence of histological abnormalities or symptoms. Furthermore, we discuss the concept that a gluten-free diet must be followed for life by all patients.