Untreated Coeliac Patients Research Articles

Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

Investigation of the frequency and significance of gastric metaplasia in duodenal biopsy materials of untreated pediatric celiac patients

Gastric (foveolar) metaplasia (GM) in the duodenum occurs in many cases where duodenitis develops histologically. However, few studies have investigated the presence of GM in celiac patients. This study aimed to determine the prevalence of GM and its relationship with clinicopathological parameters in untreated pediatric celiac patients. Duodenal biopsy specimens of 153 pediatric cases were analyzed. MUC5AC immunohistochemical staining was applied to all cases to detect GM. The patient group was evaluated in terms of the disease activity score (DAS), neutrophilic activity score (NAS), eosinophilic infiltration, and presence of intramucosal Brunner glands. The rate of GM was 53.4% in the control group and 98.8% in the patient group. GM was observed as diffuse morphology at a rate of 4.1% (n:3) in the control group and 55% (n:44) in the patient group (p<0.001). Diffuse type of GM was more frequent in girls in the patient group (p=0.03). When GM (focal/diffuse) age, DAS, NAS, and all histopathological parameters were compared, a statistically significant difference was found between diffuse GM and DAS, and NAS. (p=0.023 and p=0.039, respectively). The present study considered that duodenal neutrophilia and increased disease activity might play a role in the development of GM in celiac patients. We think that it would be appropriate to include a diffuse type of GM, which can be easily detected by immunohistochemical or histochemical methods, in pathology reports as a finding of histologically active celiac disease.

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 R\u03b1), FOXP3 and IL-6 expressions as genes affecting immune homeostasis

BackgroundCoronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients.MethodsSixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2−∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6).ResultsWhile increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them).ConclusionsAlthough untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq.

Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.

Back cover story: Eur. J. Immunol. 6'21

European Journal of ImmunologyVolume 51, Issue 6 Back CoverFree Access Back cover story: Eur. J. Immunol. 6'21 First published: 07 June 2021 https://doi.org/10.1002/eji.202170069AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Our back cover features TRAV and TRBV gene pairing of intraepithelial CD8+ αβ lymphocytes obtained from duodenal biopsies of untreated celiac disease patients. The TRAV/TRBV gene pairing is here depicted using Circos plots. The image is taken from Eggesbø et al. (pp. 1542–1545) where the authors by single-cell TCR sequencing demonstrate that TCR repertoires of celiac disease patients do not show any obvious V gene pairing preference. Furthermore, untreated celiac disease patients display a more polyclonal and diverse TCR repertoire compared to treated patients and healthy subjects. Volume51, Issue6June 2021 RelatedInformation

Celiac disease: causes, pathology, and nutritional assessment of gluten-free diet. A review

Introduction: celiac patients suffer deficiencies before and during their maintenance of a gluten-free diet. This is due to malabsorption, associated with the disease, and to non-enriched, mostly processed foods high in saturated fats and deficient in the minerals typically present in wheat. Objectives: the main objective of this review was to determine the molecular basis of celiac disease and the nutritional deficiencies that gluten-free diet entails, as well as an assessment of gluten-free diet and its nutritional deficiencies once the intestinal microvilli have been restored. Material and methods: a bibliographic search was carried out through electronic databases. The content of the review focuses on the pathogenesis of celiac disease and the assessment of gluten-free diet when established for treatment. Results: the main deficiencies that occur in untreated celiac patients are (calcium, iron, fiber, folic acid, omega-3, vitamin B12, and vitamin D). It has been observed that the quality of life of celiac patients, after starting treatment, is reduced, and this leads to low adherence to gluten-free diet. In addition, these gluten-free diets without proper follow-up by a nutritionist entail other deficits such as: an increase in the risk of cardiovascular, metabolic, overweight and obesity diseases. Conclusion: gluten-free diet, as followed by celiac patients, usually entails certain deficiencies such as group-B vitamins, vitamin D, calcium, iron, folic acid, and fiber, which is mainly due to the poor nutritional quality of gluten-free products as compared to their equivalents with gluten, and a scarce monitoring by health professionals.

Circulating microRNAs as potential non-invasive biomarkers in pediatric patients with celiac disease.

Celiac disease is an enteropathy induced by ingestion of gluten triggering an immune response in genetically predisposed individuals. MiRNAs are small non-coding RNAs that have a role as regulators of gene expression at the post transcriptional level. The aim of this study is to evaluate the possibility of using circulating miRNAs as non-invasive biomarkers in pediatric patients with celiac disease. In addition, we examine the effect of a gluten-free diet on the expression of these miRNAs in serum of CD patients. The expression pattern of miR-21 and miR-31 was estimated in serum of 25 untreated CD patients (recently diagnosed), 25 treated CD patients (on gluten-free diet) and 20 healthy controls using qRT-PCR. Our results demonstrated the significant up-regulation of microRNA-21 in the untreated celiac patients in comparison with the treated group and healthy controls. Moreover, miR-31 expression was significantly under-expressed in the untreated celiac patients in comparison with the treated group and healthy controls. Furthermore, the results showed that miR-21 expression level was significantly positively correlated with the tTG IgA auto-antibodies. In conclusion, circulating miRNA-21 and miRNA-31 could serve as potential non-invasive biomarkers for pediatric CD patients.

Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis.

Citrulline has been described as a marker of intestinal function or absorption but evidence varies according to clinical settings. The objective of this article is to examine the evidence of plasma citrulline as a marker of intestinal function and absorption in various clinical settings. Studies were examined for p values, means and standard deviations, correlation coefficients or other metrics depicting the association of citrulline with intestinal function. A random effects model was used to produce a pooled estimate. A hierarchical summary receiver operating curve model was fitted for diagnostic accuracy measures. Citrulline levels are correlated strongly with small bowel length in short bowel syndrome patients (r = 0.67). Citrulline is strongly negatively correlated (r = -0.56) with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, Crohn's disease, mucositis, acute rejection in intestinal transplantation). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and 84% respectively. Citrulline levels in untreated coeliac patients compared to controls were reduced by 10 µmol/l. Citrulline levels increase with gluten-free diet and with improvement of enteropathy. Citrulline is decreased in critical illness and sepsis. These findings allow us to advocate quite reasonably that citrulline is a marker of acute and chronic intestinal insufficiency.

Coeliac disease and the videocapsule: what have we learned till now.

Celiac disease is diagnosed in part by finding areas of pathology in the small bowel (SB) mucosa. This can often be difficult because the pathologic alterations, including atrophy of the small intestinal villi, can often be sparse and subtle. Some of the quantitative methods for detecting and measuring the presence of villous atrophy from videocapsule endoscopy (VCE) images are presented and discussed. These methods consist of static features of measurement including texture, gray level, and presence and abundance of fissures contained within each acquired image. The methods also consist of dynamic measurements including spectral analysis, and determining motion from a sequence of endoscopic images as obtained from a VCE clip. Thus far, several methods have been found useful to characterize the SB mucosa of untreated celiac disease patients versus control patients lacking villous atrophy, which have revealed significant differences in texture, frequency, and motion on analysis of VCE. In untreated celiac patients undergoing endoscopy, there tends to be greater magnitude of changes and spatial differences in textural descriptors, longer periodic components, indicating slower periodic activity, and differences in feature location, suggesting alterations in motility at areas of pathology as compared to patients without villous atrophy. Improvements in the quantitative analysis of VCE imaging in celiac patients is important to detect pathology in suspected patients, so that biopsies can be obtained from pertinent regions of the small intestinal mucosa. Improvements are also necessary so that patients with celiac disease can be monitored to evaluate the progress of mucosal healing after onset of treatment.

Extraction and processing of videocapsule data to detect and measure the presence of villous atrophy in celiac disease patients

BackgroundVideocapsule endoscopy is a relative new method to analyze the gastrointestinal tract for the presence of pathologic features. It is of relevance to detect villous atrophy in the small bowel, which is a defining symptom of celiac disease. MethodIn this tutorial, methods to extract and process videocapsule endoscopy data are elucidated. The algorithms, computer code, and paradigms to analyze image series are described in detail. The topics covered include extraction of data, analysis of texture, eigenanalysis, spectral analysis, three-dimensional projection, and estimation of motility. The basic paradigms to implement these processes are provided. ResultsExamples of successful quantitative analysis implementations for selected untreated celiac disease patients with villous atrophy versus control patients with normal villi were illustrated. Based on the implementations, it was evident that celiac patients tended to have a rougher small intestinal texture as compared with control patients. From three-dimensional projection, celiac patients exhibited larger surface protrusions emanating from the small intestinal mucosa, which may represent clumps of atrophied villi. The periodicity of small intestinal contractions tends to be slower when villous atrophy is present, and the estimated degree of motility is reduced as compared with control image series. Basis image construction suggested that fissuring and mottling of the mucosal surface is predominant in untreated celiac patients, and mostly absent in controls. ConclusionsImplementation of computerized methods, as described in this tutorial, will likely be useful for the automated detection and measurement of villous atrophy, and to map its extent along the small intestine of celiac patients.

Small intestinal bacterial overgrowth prevalence in celiac disease patients is similar in healthy subjects and lower in irritable bowel syndrome patients

BackgroundUntreated celiac disease has traditionally been linked to a greater risk for small intestinal bacterial overgrowth, but the existing evidence is inconclusive. AimsTo compare the prevalence of small intestinal bacterial overgrowth in subjects with celiac disease compared with control subjects and patients with irritable bowel syndrome. Material and methodsThe study included 15 untreated celiac disease patients, 15 subjects with irritable bowel syndrome, and 15 healthy controls. All enrolled patients underwent a lactulose breath test measuring hydrogen and methane. Small intestinal bacterial overgrowth was defined according to previously published criteria. ResultsNo differences were found in relation to age or sex. The prevalence of small intestinal bacterial overgrowth was similar between the celiac disease patients and the controls (20 vs. 13.33%, P=NS), whereas it was higher in patients with irritable bowel syndrome (66.66%, P<05). ConclusionThere was no difference in the prevalence of small intestinal bacterial overgrowth between the untreated celiac disease patients and healthy controls.

Small intestinal bacterial overgrowth prevalence in celiac disease patients is similar in healthy subjects and lower in irritable bowel syndrome patients.

Untreated celiac disease has traditionally been linked to a greater risk for small intestinal bacterial overgrowth, but the existing evidence is inconclusive. To compare the prevalence of small intestinal bacterial overgrowth in subjects with celiac disease compared with control subjects and patients with irritable bowel syndrome. The study included 15 untreated celiac disease patients, 15 subjects with irritable bowel syndrome, and 15 healthy controls. All enrolled patients underwent a lactulose breath test measuring hydrogen and methane. Small intestinal bacterial overgrowth was defined according to previously published criteria. No differences were found in relation to age or sex. The prevalence of small intestinal bacterial overgrowth was similar between the celiac disease patients and the controls (20 vs. 13.33%, P=NS), whereas it was higher in patients with irritable bowel syndrome (66.66%, P<05). There was no difference in the prevalence of small intestinal bacterial overgrowth between the untreated celiac disease patients and healthy controls.

Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease.

Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be passively transferred to mice by serum or immunoglobulins. Serum aliquots or purified immunoglobulins (Ig) were intraperitoneally injected into Hsd:Athymic Nude-Foxn1nu mice for 8 or 27 days. As mice do not have proper IgA transport from peritoneum to blood, sera with a high content of IgG class anti-TG2 antibodies from untreated IgA-deficient celiac patients were used. Mouse sera were tested for celiac disease-specific autoantibodies, and several tissues were analyzed for autoantibody deposits targeted to TG2. Morphological assessment was made of the murine small intestinal mucosa. Injection of celiac disease patient sera or total IgG led to a significant delay in weight gain and mild diarrhea in a subset of mice. The mice injected with celiac patient sera or IgG had significantly decreased villus height crypt depth (Vh/CrD) ratios and celiac disease-specific autoantibody deposits targeted to TG2 in several tissues, including the small intestine. None of these features were observed in control mice. We conclude that administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice. The experimentally induced condition in the mice injected with patient serum or IgG resembles early developing celiac disease in humans. Celiac disease patient sera or total IgG was injected into athymic mice. A significant delay in weight gain and mild diarrhea was observed. Mice evinced significantly decreased villus height crypt depth ratios. Celiac disease-specific autoantibody deposits were present in several tissues. The condition in mice resembles early stage celiac disease in humans.

Celiac mucosa still produces anti-tissue transglutaminase2 antibodies after two years of a gluten free diet

Objectives and study: Anti-tissue transglutaminase2 (anti-TG2) antibodies are present in the serum of the great majority of untreated celiac (CD) patients. These autoantibodies, produced in the small intestinal mucosa, disappear in the serum after a gluten free diet (GFD). Our aim was to investigate the production of intestinal anti-TG2 antibody in patients on a GFD using two techniques: the detection of mucosal deposits and the measurement of antibodies secreted into organ culture supernatants.

Use of shape-from-shading to estimate three-dimensional architecture in the small intestinal lumen of celiac and control patients

BackgroundAs measured from videocapsule endoscopy images, the small intestinal mucosa of untreated celiac patients has significantly greater and more varied texture compared to normal patients. Three-dimensional modeling using shape-from-shading principles may further increase classification accuracy. MethodsA sequence of 200 consecutive videocapsule images acquired at a 2s–1 frame rate and 576×576 pixel dimension, were obtained at four locations in the small intestinal lumen of ten patients with biopsy-proven celiac disease and ten control patients. Each two-dimensional image was converted to a three-dimensional architectural approximation by considering the 256 grayscale level to be linearly representative of image depth. From the resulting three-dimensional architecture, distinct luminal protrusions, representative of the macro-architecture, were automatically identified by computer algorithm. The range and number of protrusions per image, and their width and height, were determined for celiacs versus controls and tabulated as mean±SD. ResultsThe mean number of villous protrusions per image was 402.2±15.0 in celiacs versus 420.8±24.0 in controls (p<0.001). The average protrusion width was 14.7 pixels in celiacs versus 13.9 pixels in controls (p=0.01). The mean protrusion height was 3.10±2.34 grayscale levels for celiacs versus 2.70±0.43 grayscale levels for controls (p<0.001). Thus celiac patients had significantly fewer protrusions on the luminal surface of the small intestine as compared with controls, and these protrusions had greater dimensions, suggesting they are indicative of a mosaic (cobblestone) macro-architectural pattern which is common in celiacs. ConclusionsShape-from-shading modeling is useful to explore luminal macro-architecture and to detect significant differences in luminal morphology in celiac versus normal patients, which can increase the usefulness of videocapsule studies.

CYP3A4-Catalyzed Simvastatin Metabolism as a Non-Invasive Marker of Small Intestinal Health in Celiac Disease

Histological examination of duodenal biopsies is the gold standard for assessing intestinal damage in celiac disease (CD). A noninvasive marker of disease status is necessary, because obtaining duodenal biopsies is invasive and not suitable for routine monitoring of CD patients. As the small intestine is a major site of cytochrome P450 3A4 (CYP3A4) activity and also the location of the celiac lesion, we investigated whether patients with active CD display abnormal pharmacokinetics of an orally administered CYP3A4 substrate, simvastatin (SV), which could potentially be used for noninvasive assessment of their small intestinal health. Preclinical experiments were performed in CYP3A4-humanized mice to examine the feasibility of the test. Subsequently, a clinical trial was undertaken with 11 healthy volunteers, 18 newly diagnosed patients with CD, and 25 celiac patients who had followed a gluten-free diet (GFD) for more than 1 year. The maximum concentration (Cmax) of orally administered SV plus its major non-CYP3A4-derived metabolite SV acid (SV equivalent (SVeq)) was measured, and compared with clinical, histological, and serological parameters. In CYP3A4-humanized mice, a marked decrease in SV metabolism was observed in response to enteropathy. In the clinical setting, untreated celiac patients displayed a significantly higher SVeq Cmax (46±24 nM) compared with treated patients (21±16 nM, P<0.001) or healthy subjects (19±11 nM, P<0.005). SVeq Cmax correctly predicted the diagnosis in 16/18 untreated celiac patients, and also the recovery status of all follow-up patients that exhibited normal or near-normal biopsies (Marsh 0-2). All patients with abnormal SVeq Cmax showed a reduction in the value after 1 year of following a GFD. SVeq Cmax is a promising noninvasive marker for assessment of small intestinal health. Further studies are warranted to establish its clinical utility for assessing gut status of patients with CD.

PTU-199 Proinflammatory Cytokine (Il-8) in Microscopic Enteritis

IntroductionCeliac disease (CD) is an autoimmune disorder that is triggered by an immune response to gluten in genetically predisposed individuals. Interleukin-8 (IL-8) is produced by macrophages, epithelial cells and endothelial...

Tu1973 Bifidobacterium Infantis Nls Super Strain Reduces Expression of Alpha-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Untreated Celiac Patients

Tu1973 Bifidobacterium Infantis Nls Super Strain Reduces Expression of Alpha-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Untreated Celiac Patients

Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease

Anandamide (AEA) is the prominent member of the endocannabinoid family and its biological action is mediated through the binding to both type-1 (CB1) and type-2 (CB2) cannabinoid receptors (CBR). The presence of AEA and CBR in the gastrointestinal tract highlighted their pathophysiological role in several gut diseases, including celiac disease. Here, we aimed to investigate the expression of CBR at transcriptional and translational levels in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also biopsies from treated celiac patients cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our data show higher levels of both CB1 and CB2 receptors during active disease and normal CBR levels in treated celiac patients. In conclusion, we demonstrate an up-regulation of CB1 and CB2 mRNA and protein expression, that points to the therapeutic potential of targeting CBR in patients with celiac disease.

Diagnostic accuracy of a new point-of-care screening assay for celiac disease

To determine the diagnostic accuracy of a new point-of-care assay detecting anti-deamidated gliadin peptides in celiac disease (CD) patients. One-hundred-and-twelve patients (age range: 1.8-79.2 years old) with clinical symptoms suggestive of CD and/or first-degree relatives (FDR) of CD patients (n = 66), and confirmed CD on a gluten-free diet (GFD) (n = 46), were prospectively enrolled in the study at Gastroenterology outpatient clinics for adult patients and from the Gastroenterology Consultation Ward at the Pediatric Department of the University Hospital of Geneva. Written informed consent was obtained from all subjects enrolled. The study received approval from the local ethics committee. The original CD diagnosis had been based on serum-positive IgA anti-tissue transglutaminase enzyme-linked immunosorbent assay (ELISA) (QuantaLite™, Inova Diagnostics, San Diego, CA, United States) and on biopsy results. Serum samples from all study participants were tested by the new CD lateral flow immunochromatographic assay (CD-LFIA) device, Simtomax® Blood Drop (Augurix SA, BioArk, Monthey, Switzerland) to detect immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides. The diagnostic performance was evaluated using receiver operating characteristic curves with 95%CIs. A cut-off of 2 on the Rann colorimetric scale was used to calculate the device's sensitivity and specificity. CD-LFIA was highly accurate in detecting untreated celiac patients. In the group of patients with CD symptoms and/or FDR, eight new cases of CD were detected by ELISA and biopsy. All of these new cases were also correctly identified by CD-LFIA. The test yielded four false positive and four false negative results. The false positive results were all within the groups with clinical symptoms suggestive of CD and/or FDR, whereas the false negative results were all within the GFD group. The test yeld a sensitivity of 78.9% (95%CI: 54.4-93.9) and specificity of 95.7% (95%CI: 89.4-98.8), and the area under the curve reached 0.893 (95%CI: 0.798-0.988). The Kappa coefficient, calculated according to the values obtained by two readers from the same device, was of 0.96 (SE: 0.06). When the GFD patients were excluded from the analysis, the area under the curve reached 0.989 (95%CI: 0.971-1.000) and the Kappa coefficient, calculated according to the values obtained by two readers from the same device, became 0.96 (SE: 0.07). Furthermore, using the Rann scale cut-off of 2 without the GFD patients, sensitivity was 100% and specificity was 93.1% (95%CI: 83.3-98.1). The new CD-LFIA rapid screening test shows good diagnostic accuracy, sensitivity and specificity, and may rule out CD in patients with CD-related symptoms.