Celiac Disease Research Articles

Celiac Disease Increases the Risk of Multiple Sclerosis: Evidence from Mendelian Randomization and the Role of CCL19.

Celiac disease (CeD) is an autoimmune disorder triggered by gluten, primarily affecting the small intestine but potentially impacting other systems, including the nervous system through the gut-brain axis. This study employed Mendelian randomization (MR) to explore the causal relationships between CeD and several neurological disorders, with a particular focus on multiple sclerosis (MS). Utilizing genetic data from the OpenGWAS and Finngen databases, we applied various MR methods, including Inverse Variance Weighted (IVW), IVW-multiplicative random effects (MRE), weighted median (WM), MR-Egger, and robust adjusted profile score (RAPS), to investigate these associations. The analysis revealed no significant causal relationship between CeD and several other neurological disorders, but a significant positive association with MS was found (IVW OR=1.1919, 95% CI: 1.0851~1.3092, p=0.0002). Further analysis indicated that the mediator CCL19 plays a significant role in the pathway from CeD to MS, suggesting that CCL19 may be a key factor in the immune response linking these conditions. This mediation effect highlights the potential mechanism through which CeD increases the risk of developing MS. These findings emphasize the complexity of the relationship between CeD and MS, indicating the need for further research to understand these connections better and their clinical implications.

Diamino variants of piperazine-based tissue transglutaminase inhibitors.

Diamino variants of piperazine-based tissue transglutaminase inhibitors.

Clinical settings in which human leukocyte antigen typing is still useful in the diagnosis of celiac disease

Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals. It is characterized by intestinal histological damage and the production of specific autoantibodies. The latest European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2020 guidelines have excluded human leukocyte antigen (HLA) genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value, limited availability, and high cost in some countries. However, HLA genetic testing remains valuable in certain clinical contexts. This study provided practical indications for when to request and how to interpret HLA genotyping, emphasizing its continued relevance for CD diagnosis in specific cases. We also proposed a strategy for monitoring the risk of developing type 1 diabetes (T1D) in patients with CD, based on the risk stratification carried by different HLA genotypes. A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in 2012, when HLA genotyping became mandatory for the diagnosis of CD. We identified key clinical scenarios where HLA testing remains useful. Several high risk HLA-DQ genotypes strongly associated with CD were highlighted, including HLA-DQ2.5/HLA-DQ2.2 and HLA-DQ2.5/HLA-DQ2.5. Notably, while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD, it appears to confer protection against T1D. To support clinical practice, we presented a table clarifying commonly used HLA terminology, and another summarized the main clinical situations in which HLA genotyping should still be considered. These findings underscore the dual role of HLA testing: Not only can it help rule out CD in selected cases, but it also identifies patients with CD at risk for T1D, guiding personalized monitoring strategies.

Development and Quality Evaluation of Gluten-free Waffle Cone Prepared from Sorghum and Khandsari Sugar

This study explores the development of a gluten-free waffle cone using sorghum flour as a healthier and functional alternative to conventional wheat-based cones. Proximate composition analysis revealed that sorghum-based cones had enhanced nutritional properties, including higher moisture (3.1%), ash (2.4%), fat (12.5%), protein (10.2%), and crude fiber (3.2%) contents, along with reduced carbohydrate (67.2%) and energy values (442 kcal/100 g) compared to the control market cone. Sensory evaluation indicated that although the sorghum cone received slightly lower scores in appearance, texture, taste, and overall acceptability, it remained within an acceptable range, indicating good potential for consumer acceptance. These results highlight the nutritional advantages of sorghum flour in gluten-free product development. Implementation of these findings can aid in the formulation of healthier, gluten-free alternatives in commercial bakery and ice cream cone manufacturing, particularly benefiting consumers with celiac disease or gluten sensitivity, while also promoting the utilization of underused grains like sorghum. Overall, sorghum-based waffle cones offer a sustainable, nutrient-dense snack option that aligns with the rising demand for gluten-free and health-conscious food products.

Single cell transcriptome sequencing indicates the cellular heterogeneity of small intestine tissue in celiac disease

Celiac disease (CeD) is an autoimmune small intestinal disease caused by gluten protein ingestion by genetically susceptible individuals. Genome-wide association studies and transcriptomic data have limited capacity to capture intercellular genetic variations. We aimed to construct a single cell transcriptome spectrum, analyze the immune microenvironment and cellular heterogeneity, discover disease-related specific genes and markers, and explore the pathogenesis of CeD. This study performed single cell RNA sequencing (scRNA-seq) on three small intestine biopsies from patients with CeD and three matched healthy Chinese controls. Immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) were used to validate potential diagnostic biomarkers of disease-differential genes. A total of 10 cell subpopulations were annotated, including three types of epithelial and stromal cells and seven types of immune cells. IHC revealed a pronounced overexpression of T cell disease-differential genes, TRAT1, BCL11B, and ETS1 in intraepithelial lymphocytes in the CeD group. Further clinical validation using qPCR confirmed that ETS1 (P = 0.010), TRAT1 (P < 0.001), and BCL11B (P = 0.036) were enriched in the CeD small intestinal tissue. The CD28/CTLA-4 pathway regulates the homeostasis of Treg cells. The IFITs family genes may serve as marker genes for antiviral specific CD4+ T cell subsets. CeD-derived subsets of CD8+ T cells frequently express genes associated with cytotoxicity, including IFNG, GZMK, GZMH, GZMB, SH2D1A, PRF1, and NKG7, as well as genes related to T cell exhaustion, such as PDCD10, CTLA4, TIGIT, PDCD1, and DUSP4. Inflammation and infection pathways were enriched in different cell populations. A single cell expression profile of CeD small intestinal tissue was successfully constructed using scRNA-seq in this study. New biomarkers for CeD-specific histopathology and potential therapeutic targets were discovered, and the biomarkers observed between inflammation and infection pathways were closely related to the onset of CeD.

The Associations of Tobacco, Alcohol, and Coffee Consumption with Upper and Lower Gastrointestinal Disease Risk: A Mendelian Randomization Study.

Gastrointestinal diseases present a significant global health challenge and greatly impact healthcare expenditures. Despite alcohol, tobacco, and coffee being universally recognized risk factors for various gastrointestinal disorders, the exact causal linkages have not been clarified because of the predominance of observational studies on this topic. Mendelian randomization (MR) was used to explore to what extent alcohol, tobacco, and coffee increase the risk of developing 13 upper and lower gastrointestinal diseases. Genetic data from large genome-wide association studies including GSCAN, FinnGen, UK Biobank, IIBDGC, GERA, and other consortia were used for both univariable and multivariable MR analyses. Single-nucleotide polymorphisms were used as instrumental variables and sensitivity analyses were conducted to identify potential pleiotropic effects. Genetically predicted smoking was positively associated with esophageal cancer, Crohn's disease, gastric ulcer, irritable bowel syndrome, and gastroesophageal reflux risk, but was negatively associated with celiac disease risk. Alcohol intake was positively correlated with both esophageal cancer and chronic gastritis risk. These findings were confirmed by multivariable MR analyses, albeit with some variations. Coffee consumption was linked to esophageal cancer, but the association became nonsignificant after adjusting for hot beverage consumption. This comprehensive MR study suggests that alcohol and tobacco consumption are associated with the occurrence of several gastrointestinal diseases. These results support the need for public health initiatives to reduce smoking and alcohol abuse, with the aim of preventing both upper and lower gastrointestinal diseases.

Has the Rise of Celiac Disease Incidence in Estonian Children Stopped?

The aim of this study was to analyse the incidence and clinical presentation of childhood CD from 2011 to 2020 in Estonia and to compare the incidence with earlier published results of a 35-year period (1976-2010). Data was collected retrospectively about children up to 19 years of age who were newly diagnosed with CD from 2011 to 2020 in all of Estonia. CD was diagnosed mostly by biopsy and in only two cases by serology. From 2011 to 2020, 189 new CD cases were diagnosed (113 girls, 60%, M/F ratio 1:1.49). The median age at diagnosis was 8.6 years. For comparison, from 1976 to 2010, the median age was 2.3 years. There were no differences between boys and girls (p = 0.93). Most frequently, the patients had atypical gastrointestinal symptoms. The incidence rate per 100 000 person-years in 2011-2020 was 6.89 (95% CI: 5.94-7.94). For comparison, in 1976-1980, the incidence rate per 100 000 person-years was 0.1. The median age at diagnosis increased markedly during the study period. From 1976 onward, there has been almost a 70-fold increase in the incidence rate of CD.

A Case Report of Celiac Disease and Small Bowel Adenocarcinoma: Two Diseases With Similar Symptoms

A Case Report of Celiac Disease and Small Bowel Adenocarcinoma: Two Diseases With Similar Symptoms

Optimized Feature Selection and Machine Learning for Accurate Celiac Disease Diagnosis with Model Interpretability

Optimized Feature Selection and Machine Learning for Accurate Celiac Disease Diagnosis with Model Interpretability

Assessment of Mean Platelet Volume in Children with Celiac Disease on a Gluten-Free Diet

Assessment of Mean Platelet Volume in Children with Celiac Disease on a Gluten-Free Diet

Allergic and immunologic evaluation of children with celiac disease

IntroductionCeliac disease (CD) and allergic diseases are immune-mediated disorders with overlapping clinical and immunologic features. The association between CD and selective immunoglobulin (Ig) A deficiency (sIgAD) is well-established, but limited data exist on the relationship between CD, other antibody deficiencies, and allergic diseases in children. This study aimed to evaluate the prevalence of allergic manifestations and immunologic abnormalities in children with CD.MethodsThis prospective study included children with biopsy-confirmed CD, followed at a gastroenterology clinic from August 2022 to February 2023. Participants underwent comprehensive immunologic and allergic evaluation, including serum immunoglobulin levels, vaccine antibody responses, lymphocyte subgroup analysis, and allergy testing as clinically indicated.ResultsThe cohort included 76 patients with a median age of 11 years and a median age at CD diagnosis of 5.8 years. Allergic manifestations included aeroallergen sensitivity (22.4%), allergic rhinitis (15.8%), allergic conjunctivitis (13.2%), food allergy (5.3%), and asthma and eczema (3.9% each). Immunologic evaluations revealed normal profiles in 69.7% of patients, while abnormalities included partial IgM deficiency (6.6%), unclassified hypogammaglobulinemia (5.3%), sIgAD (2.6%), and transient hypogammaglobulinemia of infancy (2.6%). Elevated IgE levels were observed in 13.2% of patients.ConclusionThis study highlighted a significant prevalence of allergic diseases and immunologic abnormalities in children with CD, extending beyond the commonly recognized association with sIgAD. These findings underscore the importance of comprehensive immunologic and allergic evaluation in children with CD.

Deletion of wheat alpha-gliadins from chromosome 6D improves gluten strength and reduces immunodominant celiac disease epitopes

Wheat gliadins and glutenins confer valuable end-use characteristics but include amino acid sequences (epitopes) that can elicit celiac disease (CeD) in genetically predisposed individuals. The onset of CeD in these individuals is affected by the amount and duration of the exposure to immunogenic epitopes. Therefore, a reduction of epitopes that result in high immune responses in the majority of CeD patients (immunodominant epitopes) may reduce the incidence of CeD at a population level. We generated gamma radiation-induced deletions encompassing the α-gliadins in each of the three wheat genomes and characterized them using exome capture. These deletions, designated as Δgli-A2, Δgli-B2, and Δgli-D2, were deposited in GRIN-Global. The Δgli-A2 and Δgli-B2 deletions showed limited effects on breadmaking quality, but the Δgli-D2 deletion significantly increased gluten strength and improved breadmaking quality without compromising dough elasticity, protein content, or grain yield. The stronger effect of Δgli-D2 on gluten strength was associated with an increased proportion of glutenins and the deletion of α-gliadins with seven cysteines, which are absent in the GLI-A2 and GLI-B2 loci. We show that α-gliadins with seven cysteines are incorporated into the gluten polymer, where they likely function as chain terminators limiting the expansion of the gluten polymer and reducing its strength. In addition to its beneficial effects on breadmaking quality, the Δgli-D2 deletion eliminates major wheat immunodominant CeD epitopes. The deployment of this publicly available Δgli-D2 deletion can simultaneously improve wheat gluten strength and reduce the population-wide burden of CeD.

Frequency and Severity of Neurological Symptoms Following Gluten Exposure in Individuals with Celiac Disease (P1-2.010)

Frequency and Severity of Neurological Symptoms Following Gluten Exposure in Individuals with Celiac Disease (P1-2.010)

Can the Mucosa Heal Histologically in Celiac Disease? What are the Indicators of Remission in Celiac Patients?

Can the Mucosa Heal Histologically in Celiac Disease? What are the Indicators of Remission in Celiac Patients?

Early and sensitive diagnosis of celiac autoimmune disease by using carboxylic acid functionalized magnetic nanoparticles-assisted biosensing platform

A novel impedimetric magneto-immunosensor based on iron oxide (Fe3O4) nanoparticles coated with 3-phosphonopropionic acid (3-PPA) (functionalized magnetic beads, or FMBs) was created for the highly sensitive and selective detection of anti-tissue transglutaminase antibody (anti-tTG) in human serum. This label-less immunosensor was introduced by magnetically attaching FMBs onto the working electrode surface with a neodium magnet. The FMBs were utilized as a sensing interface and had carboxylic acid groups for tTG molecules, which could selectively link the target anti-tTG antibody. The FMBs modification steps were carried out in microcentrifuge tubes and concentrated with magnetic force before electrochemical analyses. The specific immuno-interactions on the FMBs surface were characterized by using the electrochemical and microscopic techniques, and in the presence of anti-tTG antibodies, they were captured by tTG-immobilized magnetic beads, and significant increases were observed in impedimetric response. The magneto biosensor response was linearly related to the anti-tTG antibody level in a broad linear range of 0.125–15.62 U/mL and a low detection limit (LOD) of 0.04 U/mL. Additionally, this magneto sensor was stable, repeatable, reproducible, selective, and sensitive for determination of the anti-tTG. The commercial enzyme-linked immunosorbent assay (ELISA) method was employed to compare the responses of the suggested immunosensor in actual samples. The magneto biosensor results were in good agreement with the ELISA reference technique results. Consequently, the biosensor performance in the analysis of serum samples was acceptable.Graphical

A novel ITGB2 variant in a patient with severe recurrent pyoderma gangrenosum-like lesions and underlying leukocyte adhesion deficiency type I: case report and literature review.

Leukocyte adhesion deficiency (LAD) is a group of inborn errors of immunity caused by mutations of integrin subunit b2 gene (ITGB2). Pyoderma gangrenosum (PG) is an uncommon neutrophilic dermatosis characterized by recurrent, sterile, and enlarging necrotic ulcers which may manifest as a single or multiple new lesions simultaneously. Here we report a 43-year-old woman from a consanguine marriage who was diagnosed with LAD-I in childhood, recurrent severe PG-like lesion, and atypical manifestations including celiac disease and low CD19 B-cell subsets. A targeted genetic panel revealed a novel homozygous missense variant c.988T>C (Tyr330His) in ITGB2 gene. While the treatment with prednisolone, cyclosporine, and antibiotics led to partial improvement, the patient unfortunately discontinued the therapy and later died from septicemia. Early hematopoietic cell transplantation (HCT) shortly after birth can be highly effective in managing patients with LAD and preventing life-threatening infections. However, evidence suggests that HCT does not prevent autoinflammatory and autoimmune disorders such as PG. Therefore, it is important to monitor LAD patients for the potential development of PG, even after HCT.

Assessment of Non-Cereal Products Gluten Cross-Contamination Exposure Risk in a Polish Female Population of Patients Diagnosed with Coeliac Disease.

Following gluten-free diet is challenging, due to risk of gluten cross-contamination. The study aimed to assess the non-cereal products gluten cross-contamination exposure risk in patients with coeliac disease. The study was conducted in a population of 699 Polish female members of the Polish Coeliac Society purchasing gluten-free products on-line (445 patients, 254 relatives). Participants were asked about frequency of buying and availability of gluten-free alternatives of non-cereal products characterized by the gluten cross-contamination risk ('hidden' gluten sources). The most frequently bought non-cereal gluten-free alternatives of the 'hidden' gluten sources were baking powders, spices, side dishes, ice cream, chocolate and chocolate products, snack bars and candies. The caregivers often declared buying 'often' gluten-free baking powder, snack bars, chocolate and chocolate products, candies, ice cream, as well as often declared problems with the availability of gluten-free spices, chocolate and chocolate products, while patients often declared buying 'often' gluten-free beer, as well as often declared problems with its availability. The older respondents often declared buying 'often' gluten-free baking powder, while younger respondents often declared buying 'often' gluten-free chocolate and chocolate products, as well as often declared problems with the availability of gluten-free instant soups, and beer. The respondents living in small towns/villages often declared problems with the availability of gluten-free powder sauces. The respondents not purchasing in hypermarkets often declared buying 'often' gluten-free baking powder, spices, candies. The respondents who most often purchased gluten-free products often declared problems with the availability of gluten-free side dishes, chocolate and chocolate products. The majority of patients diagnosed with coeliac disease do not buy a number of gluten-free alternatives of the 'hidden' gluten sources, so they may be prone to gluten exposure, due to non-cereal products' gluten cross-contamination risk.

Celiac Disease and Metabolic Diseases: A Review of Emerging Connections

Celiac Disease and Metabolic Diseases: A Review of Emerging Connections

Bridging the Gap: Awareness, Knowledge, and Challenges of Living with Celiac Disease in Bulgaria.

Background: Celiac disease (CD) is a chronic immune-mediated systemic disorder induced by gluten in genetically predisposed individuals, requiring lifelong management through a strict gluten-free diet (GFD). Although its global prevalence is around 1%, awareness and diagnosis remain suboptimal, contributing to challenges in disease management. Objectives: To assess the awareness, knowledge, and experiences of Bulgarian CD patients and caregivers regarding CD, diagnosis, and dietary adherence. Methods: A structured survey was conducted to evaluate patient and caregiver knowledge, awareness, and experiences with CD, focusing on the diagnostic process and dietary practices. Data were collected from a sample of Bulgarian CD patients and their caregivers. Results: The majority of the 191 respondents (94%) recognized CD as a lifelong condition, but only 26.7% correctly identified its autoimmune, systemic nature. The average diagnostic delay was 8.1 months, with over 50% of patients relying on serological tests alone, consistent with recent non-biopsy guidelines. Dietary adherence was significantly hindered by misconceptions about gluten-containing grains and societal barriers. Notably, 83.6% of participants reported bringing their own food when eating outside. Conclusions: The findings underscore the need for targeted public health initiatives, enhanced healthcare provider training, and improved dietary education to address knowledge gaps, expedite diagnosis, and improve dietary adherence. Such interventions could help reduce the psychosocial burden of CD and enhance the quality of life for affected individuals.

Early-Life Exposure to Acid-Suppressive Therapy and the Development of Celiac Disease Autoimmunity

ImportanceEarly-life use of acid-suppressive therapy has increased over the past 2 decades. Although these medications are widely used, recent studies showed an association between early-life use of acid-suppressive therapy and various long-term outcomes, including celiac disease.ObjectiveTo assess the association between early-life use of acid-suppressive therapy and the risk of celiac disease autoimmunity using 2 observational approaches on a large population-based database.Design, Setting, and ParticipantsThe cohort study took place in Israel using Maccabi Healthcare Services data. The data were collected on December 8, 2023, and were initially analyzed from January to May 2024. Analysis of the data continued during the revision rounds that took place from October 2024 to February 2025. Children born between January 1, 2005, and December 31, 2020, were included, grouped based on their exposure to acid-suppressive therapy within the first 6 months after birth and subsequently followed up for outcome development until the age of 10 years or December 8, 2023. A retrospective matched cohort design (N = 79 820) and retrospective matched test-negative case-control design (n = 24 684), including only the population tested for celiac disease autoimmunity, were used separately and compared.ExposurePrescription purchase of acid-suppressive therapy, either proton-pump inhibitors or histamine-2 receptor antagonists, during the first 6 months of life.Main Outcomes and MeasuresCeliac disease autoimmunity was defined as a positive anti–transglutaminase 2 enzyme-linked immunosorbent assay test result according to the thresholds of the commercial kits used. Time to first positive result for celiac disease autoimmunity was defined as the outcome in the cohort design, and acid-suppressive therapy use was defined as the outcome in the test-negative design.ResultsThe cohort design included 79 820 children (41 319 boys with no acid-suppressive therapy use [51.8%]; median birth year, 2015 [IQR, 2011-2018]), of whom 19 955 (25.0%) used acid-suppressive therapy. The rate of celiac disease autoimmunity was significantly higher among children using acid-suppressive therapy than among those not using acid-suppressive therapy (1.6% [310 of 19 955] vs 1.0% [610 of 59 865]; P &amp;amp;lt; .001). The adjusted hazard ratio of acid-suppressive therapy use for development of celiac disease autoimmunity was 1.52 (95% CI, 1.33-1.74). In the test-negative case-control design, a total of 24 684 children were included (62.2% girls; median birth year, 2012 [IQR, 2009-2016]), of whom 6176 (25.0%) were celiac disease autoimmunity positive. The rate of acid-suppressive therapy users among those who tested positive for celiac disease autoimmunity was not significant compared with those who tested negative (5.0% [309 of 6176] vs 4.6% [858 of 18 508]; P = .25). The adjusted odds ratio of a positive celiac disease autoimmunity test for acid-suppressive therapy use was 1.07 (95% CI, 0.94-1.23), which was nonsignificant compared with the population that tested negative.Conclusions and RelevanceThis retrospective study included both cohort and test-negative case-control designs. In the cohort design, acid-suppressive therapy was significantly associated with celiac disease autoimmunity. In the test-negative case-control design, this association was not significant. These results suggest a residual confounding by health care utilization in cohort designs studying celiac disease and suggest a noncausal association between acid-suppressive therapy and celiac disease autoimmunity.