In recent years, wheat- and gluten-free diets have increased in demand due to reported increases in various conditions reported to be driven by ingredients of these food products. Celiac disease, wheat allergy and non-celiac wheat sensitivity constitute the three main categories of wheat-related disorders. Celiac disease is a well-characterized immune-mediated disease caused by immune reaction against specific gliadin epitopes, the main protein in wheat. Screening studies of samples collected over time bring evidence that there is a true increase in prevalence not only driven by increased testing activity. Clinical presentation of CeD is diverse and there is an increased risk of autoimmune co-morbidities. Wheat allergy consists of IgE- and non-IgE-mediated reactions, driven by Th2-cells directing eosinophil and basophil responses. Rapid IgE-mediated reactions are characterized by specific IgE antibodies in conjunction with symptoms originating especially from the respiratory and gastrointestinal tract. There is an increased risk of other allergies and the majority recover during adolescence. Non-IgE-mediated wheat allergy is a less-well defined condition, which is often diagnostically challenging due to a longer interval between exposure and symptoms and lack of non-invasive biomarkers. In this condition, wheat as a trigger needs to be established by exclusion followed by dietary challenge. Non-celiac wheat sensitivity, despite being the most recently recognized, has the highest reported prevalence among the three wheat-related entities. It remains, however, particularly poorly characterized due to unclear pathophysiology and lack of diagnostic markers. This narrative review will scrutinize the shared and distinct clinical features of the three wheat-related conditions, focusing on epidemiology, clinical presentation, co-morbidities, diagnosis, treatment and prognosis.

The reported prevalence of coeliac disease (CD) in rheumatoid arthritis (RA) is variable.

To evaluate the prevalence and incidence of CD in RA and controls.

Case-control study on administrative data.

The RECord linkage On Rheumatic Disease database (administrative data, 2004-2013) was used to retrieve patients with RA and age and sex-matched controls. Prevalence and incidence of CD were calculated and stratified according to age, gender, and calendar year.

The cohort included 346,956 subjects (mean age 59.9 (14.5), 70.7% females), of which 70,061 RA and 276,895 controls. Median follow-up was 9 years (IQR 9-9). The prevalence of CD was higher in RA (171/70,061 = 0.24% (0.2-0.3%) vs 398/276895 = 0.14% (0.1-0.2%), p < 0.001). The prevalence of CD among females with RA was increased compared to controls (0.3% vs 0.08%, p < 0.001), but was not increased in males with RA. The incidence was higher in RA and remained stable throughout the observation period.

The prevalence and incidence of CD were increased in RA, particularly in females.

This study examined the prevalence of different BMI categories among newly diagnosed pediatric celiac disease (CD) patients in Israel from 2002 to 2018. A retrospective cross-sectional study using the database of Clalit Health Services in Israel included 5520 newly diagnosed CD children aged 2-18 between 2002 and 2018. Data on BMI, gender, ethnicity, and socioeconomic status (SES) were collected and analyzed Of the 5520 CD patients, 57.5% were female, 39.7% had low SES, and 77.1% were Jewish. At diagnosis, 13.1% were underweight, 73% had normal BMI, 9.1% overweight, and 4.8% were obese. Underweight and obese patients tended to be older at diagnosis (9 years) compared with normal and overweight patients (8 years) (P < 0.001). A higher proportion of Arab patients were underweight, while more Jewish patients were obese. Lower SES was significantly associated with increased underweight risk (P < 0.001). Over time, diagnosed patients had improved SES and were less underweight (P < 0.001). Male gender increased obesity risk (OR 1.36 [95% CI 1.06-1.74], P = 0.017), while Arab ethnicity was protective for obesity (OR 0.67 [95% CI, (0.45-0.99)], P = 0.047)Conclusion: Underweight prevalence significantly decreased in the second decade, but no significant change in overweight and obesity was noted. Underweight was associated with older age at diagnosis, poverty, and Arab ethnicity. Obesity was associated with older age and was more frequent in Jewish and male patients. Physicians should have a low threshold for CD screening regardless of BMI status to enable timely diagnosis and treatment to prevent long-term health consequences. What Is Known: • Celiac disease is traditionally associated with underweight due to malabsorption, but recent reports suggest an increasing prevalence of overweight and obesity in pediatric patients at diagnosis What Is New: • This study found that underweight prevalence decreased significantly over time, while overweight and obesity prevalence remained unchanged. Underweight was associated with older age, poverty, and Arab ethnicity, while obesity was more common in Jewish and male patients.

Celiac disease (CeD) affects 1-2% of the world's population. The aim of this study was to relate the incidence of CeD-related serological markers to symptoms, pathologies, and environmental exposure to wheat flour, given the number of flour mills present in the region.

Serum samples were collected from 537 inhabitants from a rural city. Levels of anti-transglutaminase (a-tTg), anti-gliadin, anti-DGP antibodies and total IgA levels were measured. Volunteers completed a questionnaire covering environmental factors, demographics, pregnancies, other diseases, symptoms, and CeD diagnosis. Geo-referencing of volunteers' homes and mills in the city was performed, and correlations between the different parameters assessed were analysed.

A CeD incidence of 1.76 % was found. However, a-tTg and a-gliadin levels were elevated in the population without CeD diagnosis (9.6 % and 30.1 %). Subjects with CD diagnosis showed diarrhoea and colic pain. Women with CeD had fewer pregnancies. Positive a-tTg and number of CeD-associated symptoms appear to correlate with proximity to flour mills.

A high prevalence of CeD-related specific antibody positivity in a rural population was found, possibly due to environmental factors related to flour mills. Further research is needed to better understand CeD's pathogenesis and its health implications.

Celiac disease (CD) is an inflammatory enteropathy that has been associated to obstetric and gynecological disorders. However, it is still not adequately tested by gynecologists due to the misconception that it is solely a gastrointestinal disease. This underestimation requires the development of targeted interventions.

This study aims to evaluate the association between CD and obstetric/gynecological complications, highlight the importance of informing patients about CD manifestations, and assess the patient satisfaction with the information provided by healthcare professionals on the disease.

A digital survey was administered to celiac women via the Italian Celiac Association's website.

We analyzed 493 questionnaires. Obstetric and gynecological disorders led to the diagnosis of CD in 11.7% of interviewed. The study revealed that untreated CD patients are more predisposed to miscarriages (41.8% vs 34% before/after diagnosis, respectively, p = 0.111), anemia in pregnancy (71.4% vs 40.4% before/after diagnosis, respectively, p < 0.001) and the risk of low birth weight (newborns weighing < 1500 g were 4.0% before and 1.1% after the gluten-free diet, p = 0.028). Women with CD, both before and after gluten-free diet, had higher infertility rates (about 19%) than the general population. Additionally, 73% of interviewees were dissatisfied with the information they received from health professionals about the reproductive implications of CD.

Our research contributes to a deeper understanding of the intersection between CD and reproductive outcomes, highlighting the main obstetric and gynecological problems related to it. It emphasizes the importance of patient's perspective and the need for greater awareness about celiac disease from healthcare workers.

Background Type I diabetes mellitus (T1DM) is a prevalent chronic illness that typically manifests in childhood. In patients who are genetically predisposed to diabetes, complex interactions between environmental and genetic factors play a role in the development of type 1 diabetes. There is proof that the onset of type 1 diabetes raises the possibility of developing additional autoimmune conditions. This has to do with the hereditary predisposition to these illnesses. As the autoimmune process in pancreatic beta cells advances, it may also impact other organs, leading to the emergence of autoimmune diseases that are either organ-specific or organ-nonspecific. Purpose The purpose of this study is to determine the prevalence of autoimmune disorders among children who are diagnosed with T1DM in Al-Ahsa, Saudi Arabia, and assess the potential impact of these conditions on other comorbidities. Methods Over the course of three years, from 2020 to 2023, children with T1DM were the subjects of this descriptive retrospective cross-sectional study conducted in the Endocrinology and Diabetes Unit of the Maternity and Children's Hospital in Al-Ahsa, Saudi Arabia. There were 281 participants in total. Clinical and laboratory research was conducted on autoimmune T1DM. Results A total of 281 T1DM children were investigated, with 59.9% being female and 43.1% being male. The mean age was 12.8 ± 3.3 years, and the mean disease duration at the end of follow-up was 6.6 ± 2.9 years. Among these participants, 5.3% were diagnosed with at least one autoimmune disease (AID). Celiac disease is the most commonly reported AID, accounting for 56.3%, followed by hypothyroidism (31.3%). An increased risk of developing AIDs was linked to significant associations between older age (>10 years old) and longer duration of DM (p<0.05). Conclusion The data show a high prevalence of autoimmune comorbidities among pediatric T1DM patients treated at our department. The findings highlight the importance of regular screenings in facilitating timely diagnosis and intervention, which is critical in promoting the well-being and normative development of pediatric patients.

The only treatment for Celiac Disease (CeD), which affects about 1% of the population, is a gluten-free diet (GFD). Studies have indicated an association between the GFD, a diminished quality of life (QOL), and maladaptive eating patterns. This study aims to explore food avoidance behaviors in adults with CeD.

This cross-sectional study assessed 50 adults with biopsy-confirmed CeD who completed validated surveys evaluating demographics, psychological factors, QOL, eating pathology, and food avoidance.

Overall CDQOL scores were good (mean: 62.7 out of 100). However, 58.0% of the participants self-elected to avoid one or more additional foods without diagnosed allergies or intolerances. Those avoiding one or more other foods had lower QOL scores (57.4 (23.2) vs. 70.2 (15.9)) compared to those only avoiding gluten (p = 0.034). The mean depression score (CESD) for the group avoiding foods beyond gluten was in the depressive range, unlike those avoiding only gluten (16.0 (4.9) vs. 13.6 (4.0), p = 0.078), with 77% of those avoiding more than gluten scoring above the CESD cut-off point of 15, indicating clinical depression.

Over half of participants (58%) reported avoiding additional foods beyond the GFD, a behavior associated with decreased QOL and increased depression.

Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations.

Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma.

Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

The incidence of celiac disease (CD) has increased rapidly in the late 20th and early 21st centuries, but there are recent reports of rates levelling off in countries with a high prevalence. The aim of this study was to investigate current trends in CD in southern Sweden.

Children and adults diagnosed with CD by biopsy or serology in the region of Skåne, southern Sweden, from 2010-2022 were included. The home address was identified through registers to analyze temporal and geographical trends.

A total of 3218 CD-patients were identified (52.2% children), the vast majority detected in clinical care but a few children by screening studies. The age-standardized incidence rate was 18.6 cases/105. The incidence decreased at a rate of -0.75 cases/105 (95% CI -1.14 to -0.35, p 0.002). The incidence among girls under 18 years almost halved throughout the study period, decreasing by -2.94 cases/105 (95% CI -4.59 to -1.29, p 0.002), while there only were small changes among men. The most common age of onset was 3-9 years. CD incidence varied by place of living and was more common in small towns than urban or rural areas.

The incidence of CD in southern Sweden is decreasing, primarily in children and women who traditionally have had the highest risk of CD. CD was diagnosed most frequently in children 3-9 years old. There were regional variations in incidence. CD was most common in small towns, pointing to the importance of environmental factors in CD etiology.

Celiac disease is a common chronic inflammatory condition of the small bowel triggered by gluten in wheat, rye and barley in the diet. Non-celiac gluten sensitivity presents with symptoms similar to celiac disease with the ingestion of gluten or other components of wheat. In this article, we review challenges presented by a gluten free diet for the treatment of both disorders.

Wheat is ubiquitous in the diet and medications/products. A registered dietitian is mandatory for patient education on the gluten free diet. Naturally gluten free foods provide a healthy diet for those with celiac disease. Whole grains labelled gluten free, including oats, are encouraged in the diet as refined grains may be deficient in fiber, protein, and micronutrients, particularly folate. Gluten contamination is the most common cause of persistent symptoms in celiac disease though shared equipment of food preparation may not be as large a problem as suspected. Most with celiac disease on a gluten free diet will fully recover and gain weight that poses a problem for those overweight to start. The gluten free diet may have a negative impact on quality of life for both celiac patients and their families. Those with hypervigilance of the gluten free diet and avoidance of dining out have the lowest quality of life. The gluten free diet is currently the only effective treatment for celiac disease. A registered dietitian is needed to educate patients on the complexity of the gluten free diet with a goal of healthy eating, maintaining a healthy weight, and avoiding disordered eating or diet hypervigilance; key to a good quality of life.

Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.

This study aimed to determine the total prevalence of celiac disease (CeD), including undiagnosed cases, in a population-based study of adults screened for CeD.

The study used the fourth Trøndelag Health Study (HUNT4), conducted in 2017-2019, where 56,042 adult (aged >20 years) residents of Nord-Trøndelag County, Norway, participated. Serum samples from 54,505 participants were analyzed for anti-transglutaminase 2 IgA and IgG. Seropositive individuals were invited for a clinical assessment, including upper endoscopy with duodenal biopsies. Previously diagnosed and seronegative CeD cases were identified through linkage to hospital records and the Norwegian Patient Registry.

The rate of CeD seropositivity was 2.0% (1107/54,505). Out of these, 724 individuals attended the clinical assessment. Additionally, the hospital records and registry identified individuals with a known CeD diagnosis, that were seronegative or without serology in HUNT4 or seropositive in HUNT4 but did not participate in the clinical assessment. In total, the study confirmed a new CeD diagnosis after participation in HUNT4 in 470 individuals and a known CeD diagnosis before participation in HUNT4 in 383 individuals. The total biopsy-confirmed prevalence of CeD was 1.5% (853/56,042), and the ratio of new, previously undiagnosed CeD cases (after HUNT4) to known, previously diagnosed CeD cases (before HUNT4) was 1.2:1 (470/383).

The total prevalence of CeD in this population-based study of adults in Norway was high and many individuals were previously undiagnosed. Detection of CeD should be improved, because early diagnosis is crucial for effective management and prevention of complications.

It is a retrospective study and all samples received in the laboratory from symptomatic patients for estimation of Immunoglobulin A (IgA) antitissue transglutaminase (IgA anti-tTGA) antibodies are included. Seroprevalence of celiac disease was determined using indirect enzyme-linked immunosorbent assay for IgA anti-tTGA. Out of 8787 serum samples received in the laboratory over a period of four years, the seroprevalence of CD was 2.1, 1.62, 0.72, and 3.3%, respectively.

Celiac disease (CeD) is a chronic autoimmune condition driven by gluten ingestion in genetically predisposed individuals, resulting in inflammatory lesions in the proximal small intestine. Although the presence of specific HLA-linked haplotypes and gluten consumption are necessary for disease development, they alone do not account for the variable onset of CeD in susceptible individuals. This review explores the multifaceted role of non-host factors in CeD development, including dietary and microbial influences. We discuss clinical associations and observations highlighting the impact of these factors on disease onset and severity. Furthermore, we discuss studies in CeD-relevant animal models that offer mechanistic insights into how diet, the microbiome, and enteric infections modulate CeD pathogenesis. Finally, we address the clinical implications and therapeutic potential of understanding these cofactors offering a promising avenue for preventive and therapeutic interventions in CeD management.

Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (VCIEL) can improve accuracy and statistical precision for assessing histology, compared with individual measures.

The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IEL were compared with those for VCIEL with regards to clinical significance (effect size) and statistical significance.

For the ALV003-1021 trial, we observed an effect size and P value (analysis of covariance) of 1.37 and 0.038 for ΔVh:Cd, 1.17 and 0.005 for ΔIEL, and 1.86 and 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76 and 0.057 for ΔVh:Cd, 0.98 and 0.018 for ΔIEL, and 1.14 and 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a nontherapeutic gluten challenge study.

The composite VCIEL scale combining Vh:Cd and IEL values seems to improve accuracy and statistical precision compared with either component alone.

Globally, approximately 1.4% of people have celiac disease (CD), induced by gluten sensitivity. If left untreated, it causes small intestinal inflammation and villous atrophy, which can result in failure to thrive, anemia, osteoporosis, malabsorption, and even malignancy. The only treatment option available is a gluten-free diet (GFD). Few studies have looked at the role and perception of telehealth in relation to CD and selective nutrition both before and after the COVID-19 pandemic.

Our goal was to screen and investigate the research conducted both before and after the COVID-19 pandemic concerning the utilization of telehealth applications and solutions in CD and other GFD-dependent circumstances.

We employed a narrative review approach to explore articles that were published in scholarly journals or organizations between the years 2000 and 2024. Only English-language publications were included. PubMed and Google Scholar searches were mainly conducted using the following keywords: telemedicine, telehealth, telecare, eHealth, m-health, COVID-19, SARS-CoV-2, celiac disease, and gluten-free diet (GFD). Manual searches of the references in the acquired literature were also carried out, along with the authors' own personal contributions of their knowledge and proficiency in this field.

Only a few studies conducted prior to the COVID-19 outbreak examined the viewpoints and experiences of adult patients with CD with relation to in-person clinic visits, as well as other options such as telehealth. The majority of patients believed that phone consultations were appropriate and beneficial. Video conferencing and telemedicine became more popular during the COVID-19 pandemic, demonstrating the effectiveness of using these technologies for CD on a global basis. In recent years, urine assays for gluten identification have become accessible for use at home. These tests could be helpful for CD monitoring with telemedicine assistance.

The extended knowledge gathered from the COVID-19 pandemic is expected to complement pre-COVID-19 data supporting the usefulness of telemedicine even after the emergent pandemic, encouraging its wider adoption in standard clinical practice. The monitoring and follow-up of CD patients and other GFD-dependent conditions can greatly benefit from telemedicine.

The prevalence of coeliac disease doubled in Finland from 1980 to 2000.

To investigate whether this increase is continuing and if there are specific patient-related factors predicting the development of coeliac disease at a population level.

We elicited comprehensive health data in the nationwide Health 2000 and Health 2011 surveys. Serum samples were taken for the measurement of tissue transglutaminase antibodies (TGA); subjects who were seropositive were tested for endomysial antibodies (EmA). Coeliac disease was defined either as a reported diagnosis or as positive TGA and EmA. The surveys comprised, respectively, 6379 and 4056 individuals, forming representative samples for 2,946,057 and 2,079,438 Finnish adults. Altogether 3254 individuals participating in both surveys comprised a prospective follow-up cohort.

Prevalence of coeliac disease was 2.12% in 2000 and 2.40% in 2011 (p = 0.156). In the prospective cohort, 16 out of the 3254 (0.49%) subjects developed coeliac disease during follow-up from 2000 to 2011, with an annual incidence rate of 45 per 100,000 persons. Positive TGA without EmA (OR: 133, 95% CI: 30.3-584), TGA values in the upper normal range (51.1, 16.0-163), and after adjusting for TGA, previous autoimmune co-morbidity (8.39, 4.98-35.9) in 2000 increased the likelihood of subsequent coeliac disease.

The nationwide prevalence of coeliac disease kept on rising from 2.12% in 2000 to 2.40% in 2011 in Finland. Positive TGA without EmA, TGA titres in the upper normal range and a pre-existing autoimmune disease predisposed to coeliac disease during the 10-year follow-up.

Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only two converted from seronegative to seropositive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN = 4 units/mL) vs. tTG-IgA (non-recombinant, ULN = 20 units). There is a strong correlation between both measurements as evidenced by a Pearson coefficient of R = 0.8584; however, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of three instead of four for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.

Celiac disease (CD) is an autoimmune disease caused by an abnormal immune response triggered by ingestion of gluten. Treatment of CD is a lifelong gluten-free diet. Both diagnosed and undiagnosed CD has been found to be associated with reduced bone mineral density, which can lead to an increased risk of fractures. We therefore aimed to investigate the association of CD and the risk of fractures and osteoporosis in Denmark in a nationwide registry-based study. We identified all patients with CD (ICD-10 code K90.0) between 2000 and 2018 and included those with at least two contacts with a CD diagnosis. In total, 9397 CD patients and 93,964 randomly selected age- and sex-matched (1:10) references from the general population were identified. The overall hazard ratio (HR) of developing osteoporosis in CD patients compared with matches was 5.39 (95 % confidence interval (CI): 4.89, 5.95), however when excluding events of osteoporosis occurring within 12 months from the date of diagnosis the overall HR was reduced to 3.87 (95 % CI: 3.44, 4.33). The HR for major osteoporotic fractures was 1.37 (95 % CI: 1.25, 1.51) and for any fractures 1.27 (95 % CI: 1.18, 1.36). For osteoporosis, major osteoporotic fractures, and any fracture prior to diagnosis of CD the odds ratios comparing CD patients with matches were 4.32 (95 % CI: 3.64, 4.68), 1.29 (95 % CI: 1.21, 1.37) and 1.34 (95 % CI: 1.27, 1.41), respectively. Thus, this study showed an increased risk of osteoporosis and bone fractures among individuals with CD, both before and after diagnosis of CD. These results underline that the risk of osteoporosis should be considered in the clinical management of patients with CD and that early diagnosis and treatment could be important.

It is 40 years since the discovery of Helicobacter pylori infection. Over that time major changes have occurred in esophagogastroduodenoscopy (EGD) findings. The aim of this review is to describe these changes, and the important role H. pylori infection has played in their evolution.

References were identified through searches of PubMed using the search terms-endoscopy time trends, peptic ulcer disease, gastroesophageal reflux disease, upper gastrointestinal cancer, gastric polyps, H. pylori, eosinophilic gastrointestinal disorders, and celiac disease, from 1970 through December 2021.

The prevalence of H. pylori infection has fallen and consequently, H. pylori-positive peptic ulcer disease has become rare. Gastroesophageal reflux disease is now the commonest disorder diagnosed at EGD, and Barrett's esophagus has increased in parallel. Cancer of the distal stomach has fallen while esophageal adenocarcinoma and reflux-related cardia cancer have risen. Gastric polyps have changed from hyperplastic and adenomas to sporadic fundic gland polyps. Antimicrobial resistance has made H. pylori infection more difficult to eradicate. Eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, have emerged as important new allergic disorders. Celiac disease has changed and increased.

EGD findings appear to have changed from features suggesting a H. pylori-positive "phenotype" 40 years ago to a H. pylori-negative "phenotype" today. These changes have major implications for the management of gastrointestinal disorders.

Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4+ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8+ α/β intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRβ-rearrangements derived from gluten-specific CD4+ T-cells and gluten-triggered peripheral blood CD8+ T-cells. We show, that in addition to TCRs from gluten-specific CD4+ T-cells, TCRs of gluten-triggered CD8+ T-cells are significantly enriched in CeD duodenal tissue samples. TCRβ-rearrangements of gluten-triggered CD8+ T-cells were even more expanded in patients than TCRs from gluten-specific CD4+ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.

Celiac disease is a global disease requiring genetic susceptibility and gluten exposure to trigger immune-mediated enteropathy. The effect of the degree of gluten-containing grain availability on celiac disease prevalence is unknown. Our objective was to compare country-based gluten availability to celiac prevalence using a systematic literature review. We searched MEDLINE, Embase, Cochrane, and Scopus until May 2021. We included population-based serum screening with confirmatory testing (second serological study or small intestine biopsy) and excluded specific, high-risk, or referral populations. We determined country-specific gluten availability using the United Nations food balance for wheat, barley, and rye. Human leukocyte antigen (HLA) frequencies were obtained from allelefrequencies.net. The primary outcome was association between gluten-containing grain availability and celiac disease prevalence. Generalized linear mixed models method with Poisson's link was used for analysis. We identified 5641 articles and included 120 studies on 427 146 subjects from 41 countries. Celiac disease prevalence was 0-3.1%, median 0.75% (interquartile range 0.35, 1.22). Median wheat supply was 246 g/capita/day (interquartile range 214.8, 360.7). The risk ratio (RR) for wheat availability on celiac disease was 1.002 (95% confidence interval [CI]: 1.0001, 1.004, P = 0.036). A protective association was seen with barley, RR 0.973 (95% CI: 0.956, 0.99, P = 0.003), and rye, RR 0.989 (95% CI: 0.982, 0.997, P = 0.006). The RR for gross domestic product on celiac disease prevalence was 1.009 (95% CI: 1.005, 1.014, P < 0.001). The RR for HLA-DQ2 was 0.982 (95% CI: 0.979, 0.986, P < 0.001), and that for HLA-DQ8 was 0.957 (95% CI: 0.950, 0.964, P < 0.001). In this geo-epidemiologic study, gluten-containing grain availability showed mixed associations with celiac disease prevalence.

Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.

Celiac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD.

All patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016-2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden.

During the Covid-19 pandemic (March 2020 - December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 - February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 - -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD - 1.3, 95% CI -8.5-5.9, p = 0.75).

Our results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. In rare cases, CD may occur with a severe potential life-threatening manifestation known as a celiac crisis (CC). This may be a consequence of a delayed diagnosis and expose patients to possible fatal complications. We report the case of a 22-month-old child admitted to our hospital for a CC characterized by weight loss, vomiting, and diarrhea associated with a malnutrition state. Early identification of symptoms of CC is essential to provide a prompt diagnosis and management.

Coeliac disease (CD) is a life-long food-related disorder with a global prevalence of approximately 1%. Patients with CD often experience reduced health-related quality of life that could improve with a strict adherence to a gluten-free diet (GFD).

To obtain visual analogue scale (VAS), time trade-off (TTO) and willingness-to-pay (WTP) values amongst patients with CD.

In 2020-2021, a cross-sectional online survey was conducted amongst 312 adult CD patients in Hungary. Patients completed the Gastrointestinal Symptom Rating Scale (GSRS) and evaluated their current health and three hypothetical health state vignettes defined based on dietary adherence using VAS, conventional 10-year TTO and WTP. Multivariate regressions were used to explore the effect of patients' demographic and clinical characteristics on utility and WTP values.

Mean VAS values for current health and 'CD with strict adherence to GFD', 'CD with loose adherence to GFD' and 'CD without GFD' hypothetical health states were 79.69 ± 18.52, 85.36 ± 16.18, 62.44 ± 19.91 and 36.69 ± 25.83, respectively. Corresponding mean TTO utilities were: 0.90 ± 0.19, 0.91 ± 0.20, 0.87 ± 0.23 and 0.76 ± 0.29. Mean annual WTP values for returning to full health were: €845 ± 1077, €648 ± 1002, €862 ± 1135 and €1251 ± 1496. Older age at diagnosis, male sex, more severe gastrointestinal symptoms (GSRS) and having comorbidities were associated with lower VAS and TTO or higher WTP values for current own health (p < 0.05).

This is the first study to report TTO utilities for CD health states. Strict adherence to the GFD may result in substantial health gains in symptomatic patients. Utilities and WTP results can be used to estimate benefits of GFD in cost-utility and cost-benefit analyses.

Autoimmune diseases are thought to develop as a consequence of various environmental and genetic factors, each of which contributes to dysfunctional immune responses and/or a breakdown in immunological tolerance towards native structures. Molecular mimicry by microbial components is among the environmental factors thought to promote a breakdown in immune tolerance, particularly through the presence of cross-reactive epitopes shared with the human host. While resident members of the microbiome are essential promoters of human health through immunomodulation, defence against pathogenic colonisation and conversion of dietary fibre into nutritional resources for host tissues, there may be an underappreciated role of these microbes in the aetiology and/or progression of autoimmune disease. An increasing number of molecular mimics are being identified amongst the anaerobic microbiota which structurally resemble endogenous components and, in some cases, for example the human ubiquitin mimic of Bacteroides fragilis and DNA methyltransferase of Roseburia intestinalis, have been associated with promoting antibody profiles characteristic of autoimmune diseases. The persistent exposure of molecular mimics from the microbiota to the human immune system is likely to be involved in autoantibody production that contributes to the pathologies associated with immune-mediated inflammatory disorders. Here-in, examples of molecular mimics that have been identified among resident members of the human microbiome and their ability to induce autoimmune disease through cross-reactive autoantibody production are discussed. Improved awareness of the molecular mimics that exist among human colonisers will help elucidate the mechanisms involved in the breakdown of immune tolerance that ultimately lead to chronic inflammation and downstream disease.

Obesity is a significant risk factor for many pathological conditions. Whether a gluten-free diet (GFD) is a risk factor for overweight or obesity remains controversial.

The primary aim of this study was to assess the prevalence of body mass index (BMI) categories at disease presentation and the variation in BMI category from underweight/normal to overweight/obese and vice versa during a GFD.

PubMed, Scopus, and Web of Science databases were searched through February 2021 for retrospective, cross-sectional, and prospective studies reporting BMI categories at disease diagnosis and during a GFD.

Data were extracted by 2 reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, if necessary. Risk of bias was assessed with the Cochrane ROBINS-I tool.

Subgroup analysis based on age (pediatric/adult patients), study design (prospective, cross-sectional, retrospective), and duration of GFD was performed.. Forty-five studies were selected (7959 patients with celiac disease and 20 524 healthy controls). The mean BMI of celiac patients at presentation was significantly lower than that of controls (P < 0.001). During a GFD, the mean BMI increased significantly (mean difference = 1.14 kg/m2 [95%CI, 0.68-1.60 kg/m2]; I2 = 82.8%; P < 0.001), but only 9% of patients (95%CI, 7%-12%; I2 = 80.0%) changed from the underweight/normal BMI category to the overweight/obese category, while 20% (95%CI, 11%-29%; I2 = 85.8%) moved into a lower BMI category.

Most celiac patients had a normal BMI at presentation, although the mean BMI was significantly lower than that of controls. A GFD does not increase the risk of becoming overweight/obese, especially in children. The quality of several studies was suboptimal, with moderate or high overall risk of bias and heterogeneity.

Celiac disease has an increasing incidence worldwide and is treated with lifelong adherence to a gluten-free diet. We aimed to describe gluten-free diet adherence rates in children with screening-identified celiac disease, determine adherence-related factors, and compare adherence to food records in a multinational prospective birth cohort study.

Children in The Environmental Determinants of Diabetes in the Young study with celiac disease were included. Subjects had at least annual measurement of adherence (parent-report) and completed 3-day food records. Descriptive statistics, t-tests, Kruskal-Wallis tests and multivariable logistic and linear regression were employed.

Two hundred ninety (73%) and 199 (67%) of subjects were always adherent to a gluten-free diet at 2 and 5 years post celiac disease diagnosis respectively. The percentage of children with variable adherence increased from 1% at 2 years to 15% at 5 years. Children with a first-degree relative with celiac disease were more likely to be adherent to the gluten-free diet. Gluten intake on food records could not differentiate adherent from nonadherent subjects. Adherent children from the United States had more gluten intake based on food records than European children (P < .001 and P = .007 at 2 and 5 years respectively).

Approximately three-quarters of children with screening-identified celiac disease remain strictly adherent to a gluten-free diet over time. There are no identifiable features associated with adherence aside from having a first-degree relative with celiac disease. Despite good parent-reported adherence, children from the United States have more gluten intake when assessed by food records. Studies on markers of gluten-free diet adherence, sources of gluten exposure (particularly in the United States), and effects of adherence on mucosal healing are needed.

Celiac disease with its endoscopic manifestation of villous atrophy (VA) is underdiagnosed worldwide. The application of artificial intelligence (AI) for the macroscopic detection of VA at routine EGD may improve diagnostic performance.

A dataset of 858 endoscopic images of 182 patients with VA and 846 images from 323 patients with normal duodenal mucosa was collected and used to train a ResNet18 deep learning model to detect VA. An external dataset was used to test the algorithm, in addition to 6 fellows and 4 board-certified gastroenterologists. Fellows could consult the AI algorithm's result during the test. From their consultation distribution, a stratification of test images into "easy" and "difficult" was performed and used for classified performance measurement.

External validation of the AI algorithm yielded values of 90%, 76%, and 84% for sensitivity, specificity, and accuracy, respectively. Fellows scored corresponding values of 63%, 72%, and 67% and experts scored 72%, 69%, and 71%, respectively. AI consultation significantly improved all trainee performance statistics. Although fellows and experts showed significantly lower performance for difficult images, the performance of the AI algorithm was stable.

In this study, an AI algorithm outperformed endoscopy fellows and experts in the detection of VA on endoscopic still images. AI decision support significantly improved the performance of nonexpert endoscopists. The stable performance on difficult images suggests a further positive add-on effect in challenging cases.

This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.

Celiac disease (CeD) is associated with type 1 diabetes mellitus (T1DM), and both have the same genetic background. Most patients with T1DM who develop CeD are either asymptomatic or have mild CeD-related gastrointestinal symptoms. Therefore, children affected by T1DM should undergo screening for asymptomatic CeD. The aim of this review is to highlight the influence of a gluten-free diet (GFD) on glycemic control, growth rate, microvascular complications, and quality of life in patients with T1DM and CeD. PubMed, Google Scholar, Web of Science, and Cochrane Central databases were searched. Reports reviewed were those published from 1969 to 2022 that focused on the interplay of T1DM and CeD and examined the effect of diet on glycemic control, growth rate, and quality of life. The most challenging aspect for a child with T1DM and CeD is that most GFD foods have a high glycemic index, while low glycemic index foods are recommended for T1DM. Interestingly, dietary therapy for CeD could improve the elevated HbA1c levels. Avoiding gluten added to a diabetic dietary regimen in T1DM patients might impose practical limitations and lead to important restrictions in the lifestyle of a young patient. Consequently, non-adherence to GFD in patients with T1DM and CeD is common. GFD in patients with T1DM and CeD seems to lower the incidence of micro- and macrovascular complications, but this requires further investigation. It seems that adherence to GFD in young patients with T1DM and CeD leads to regular growth and a stable body mass index without any negative effect on HbA1c or insulin requirements. Furthermore, the lipid profile and quality of life seem to have improved with the introduction of GFD.

Red cell distribution width (RDW) could be of interest by its potential use in the assessment of celiac disorder (CD). The main objective of this study was to evaluate the case positive rate of CD and the utility of red cell distribution width (RDW) in the CD diagnosis. This prospective study included 9.066 middle adult (≥45 years old) and elderly patients (≥60 years old) from 2012 to 2021. CD diagnosis was performed by CD antibody tests (serology and Human Leucocyte Antigen genotype (HLA)) and biopsy. Gastrointestinal and extra-intestinal manifestations as well as hematological and biochemical parameters were analyzed. CD diagnoses were confirmed in 101 patients (median (IQR) age = 62 (52.3−73); 68.32% women) by serologic tests (100%) and intestinal biopsy (88.12%), showing mainly marked or complete atrophy (76.24%, MARSH 3a−c). Anemia was the most commonly presenting extra-intestinal manifestation (28.57%). Among 8975 individuals without CD, 168 age and sex matched were included. By comparison of CD and no CD individuals, we observed that high >14.3% RDW was exhibited by 58.40% and 35.2% individuals with CD and without CD, respectively. Furthermore, high RDW is associated with CD and grade III atrophy. We suggest that RDW could be used as a CD screening criterion.

Gluten ingestion in patients with celiac disease can lead to gastrointestinal symptoms and small intestinal mucosal injury.

This gluten challenge phase 2 trial was double blind and placebo controlled, and it assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth was the primary endpoint. Secondary endpoints included density of intraepithelial lymphocytes and symptom severity. These endpoints were evaluated by analysis of covariance. Additional endpoints included serology and gluten-immunogenic peptides in urine.

Fifty patients were randomized, and 43 patients completed the study (IMGX003, n = 21; placebo, n = 22). The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was -0.04 vs -0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). The mean change (worsening) in symptom severity in relative units (secondary endpoint) for IMGX003 vs placebo was 0.22 vs 1.63 (abdominal pain, P = .231), 0.96 vs 3.29 (bloating, P = .204), and 0.02 vs 3.20 (tiredness, P = .113). The 3 × 2-week trend line significance values for these symptoms, respectively, were P = .014, .030, and .002.

IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity. (ClinicalTrials.gov, Number: NCT03585478).

Celiac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients.

Adult CeD patients (n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID.

Altogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, p = 0.010) and had more joint symptoms (9.1 vs. 4.2%, p = 0.011), whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health (median score 12 vs. 14, p < 0.001) in PGWB, more overall gastrointestinal symptoms (2.1 vs. 1.9, p = 0.001), and constipation (2.0 vs. 1.7, p < 0.001) in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up.

Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support.

Celiac disease (CD) management is based on a lifelong gluten-free diet (GFD) that affects the quality of life (QoL) of patients with CD. Specific instruments have been used to evaluate this QoL, such as the CD-Questionnaire (CD-Q). This study aimed to translate, validate, and cross-culturally adapt the CD-Q in an Arabic version and then apply it to evaluate the QoL of Moroccan adult patients with CD.

The Moroccan version of the CD-Q (M-CD-Q) was administered to 150 patients with CD, and 112 of them completed it. The reproducibility and reliability of the M-CD-Q were studied by the intraclass coefficient (ICC) and Cronbach's α, respectively. Parametric and nonparametric tests, confirmatory factor analysis, and Spearman correlation were used for the statistical analysis performed by SPSS, and the goodness-of-fit test was determined using SPSS AMOS.

No difficulties were found during the translation and cultural adaptation of the CD-Q. Cronbach's α showed good internal consistency. The retest showed excellent reproducibility (ICC > 0.4). The study of the psychometric properties of the M-CD-Q showed good acceptance, zero ceiling effect, and floor effect. The model fit was good [(root mean square error of approximation = 0.075 (<0.08) and χ2 = 509.04, p < 0.001]. The total scores showed a neutral QoL. This QoL was worse in the worries subscale, which is related to gluten-free products. The GFD did not improve the QoL of the examined samples.

The M-CD-Q is the first reliable and adapted instrument in an Arab country for the evaluation of QoL in patients with CD. CD negatively influences this QoL, especially items related to gluten-free products.

Celiac disease is an immune-mediated intestinal disorder that results from loss of oral tolerance (LOT) to dietary gluten. Reovirus elicits inflammatory Th1 cells and suppresses Treg responses to dietary antigen in a strain-dependent manner. Strain type 1 Lang (T1L) breaks oral tolerance, while strain type 3 Dearing reassortant virus (T3D-RV) does not. We discovered that intestinal infection by T1L in mice leads to the recruitment and activation of NK cells in mesenteric lymph nodes (MLNs) in a type I IFN-dependent manner. Once activated following infection, NK cells produce type II IFN and contribute to IFN-stimulated gene expression in the MLNs, which in turn induces inflammatory DC and T cell responses. Immune depletion of NK cells impairs T1L-induced LOT to newly introduced food antigen. These studies indicate that NK cells modulate the response to dietary antigen in the presence of a viral infection.

Coeliac disease (CD) is a frequent immune enteropathy induced by gluten in genetically predisposed individuals. Its pathogenesis has been extensively studied and CD has emerged as a model disease to decipher how the interplay between environmental and genetic factors can predispose to autoimmunity and promote lymphomagenesis. The keystone event is the activation of a gluten-specific immune response that is driven by molecular interactions between gluten, the indispensable environmental factor, HLA-DQ2/8, the main predisposing genetic factor and transglutaminase 2, the CD-specific autoantigen. The antigluten response is however not sufficient to induce epithelial damage which requires the activation of cytotoxic CD8+ intraepithelial lymphocytes (IEL). In a plausible scenario, cooperation between cytokines released by gluten-specific CD4+ T cells and interleukin-15 produced in excess in the coeliac gut, licenses the autoimmune-like attack of the gut epithelium, likely via sustained activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway in IEL. Demonstration that lymphomas complicating CD arise from IEL that have acquired gain-of-function JAK1 or STAT3 mutations stresses the key role of this pathway and explains how gluten-driven chronic inflammation may promote this rare but most severe complication. If our understanding of CD pathogenesis has considerably progressed, several questions and challenges remain. One unsolved question concerns the considerable variability in disease penetrance, severity and presentation, pointing to the role of additional genetic and environmental factors that remain however uneasy to untangle and hierarchize. A current challenge is to transfer the considerable mechanistic insight gained into CD pathogenesis into benefits for the patients, notably to alleviate the gluten-free diet, a burden for many patients.