Gluten Exposure Research Articles

Lack of Effect of Gluten Challenge on Fecal Microbiome in Patients With Celiac Disease and Non-Celiac Gluten Sensitivity.

INTRODUCTION:Celiac disease (CD) may be associated with gut microbial dysbiosis. Whether discrete gluten exposure in subjects with well-controlled disease on a gluten-free diet impacts the gut microbiome is unknown and may have implications for understanding disease activity and symptoms. We conducted a prospective study to evaluate the impact of gluten exposure on the gut microbiome in patients with CD and nonceliac gluten sensitivity (NCGS).METHODS:Subjects with CD (n = 9) and NCGS (n = 8) previously on a gluten-free diet were administered a 14-day gluten challenge (5 g of gluten per day) and compared with controls (n = 8) on a usual gluten-containing diet. Stool was collected for fecal microbiome analysis using 16S rRNA gene and metagenomic sequencing before, during, and after the gluten challenge. Symptoms were assessed using 2 validated clinical scales.RESULTS:Among subjects with CD and NCGS, there were no significant fecal microbial changes in response to gluten challenge. Gut microbiome composition differed among controls, subjects with CD, and subjects with NCGS at baseline, and these differences persisted despite gluten exposure. Gastrointestinal and general health symptoms reported by subjects with CD and NCGS were worst in the middle of gluten challenge and lessened by its end, with no consistent associations with gut microbiome composition.DISCUSSION:Pre-existing fecal microbiome diversity was unaffected by gluten challenge in adult subjects with CD and NCGS. These findings suggest that current microbiome status is unrelated to current disease activity and disease severity.

Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity

Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

CASE REPORT: COEXISTENCE OF CELIAC DISEASE AND MULTIPLE MYELOMA

Celiac disease is a systemic disease in which the natural and adaptive immune system is affected by the effect of gluten exposure and environmental factors in individuals with genetic predisposition. Multiple myeloma; is characterized by an increase in clonal plasma cells. It is the most common hematological malignancy after lymphomas.We aimed to present a case siagnosed with celiac disease and multipl myeloma A 56-year-old female patient with a diagnosis of asthma and celiac disease for 1 year was referred to the Hematology department because her refractory anemia. Serum IgA level of the patient was 4490 mg/dl without renal failure and hypercalcemia.bone marrow biopsy compatible with myeloma. The patient received 6 cycles of bortezomib, cyclophosphamide, and dexamethasone and 3 cycles lenalidomid dexametazon chemotherapy.After chemotherapy, Autologous stem cell transplantation was performed. Celiac disease is an autoimmune disease, characterized by inflammation and villus atrophy in the small intestine mucosa as a result of sensitivity to gluten, resulting in malabsorption. The incidence of lymphoma and gastrointestinal system malignancy is increased in individuals with celiac disease. Multiple myeloma may also be accompanied by autoimmune diseases such as ankylosing spondylitis, scleroderma, and sjögren's syndrome. Coexistence of multiple myeloma and celiac disease is rare.

Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review.

BACKGROUNDGluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease (CeD). Gluten immunogenic peptides (GIP) are resistant to gastrointestinal digestion and are then excreted via the stool and urine. Most common detection methods applied in the follow-up visits for CeD patients such as serology tests, dietetic interviews, questionnaires, and duodenal biopsy have been proved to be inefficient, invasive, or inaccurate for evaluating gluten-free diet (GFD) compliance. Determination of excreted GIP in stool and urine has been developed as a non-invasive, direct, and specific test for GFD monitoring. AIMTo summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD monitoring.METHODSPubMed and Web of Science searches were performed using the keywords “gluten immunogenic peptides” or “gluten immunogenic peptide” and a combination of the previous terms with “feces”, “stools”, “urine”, “celiac disease”, “gluten-free diet”, and “adherence” to identify relevant clinical studies published in English and Spanish between 2012 to January 2021. Reference lists from the articles were reviewed to identify additional pertinent articles. Published articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with CeD in comparison with other tools in use were included. Case reports, commentaries, reviews, conference papers, letters, and publications that did not focus on the aims of this review were excluded. RESULTSTotal of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other tools. Studies included both children and adults diagnosed with CeD and healthy volunteers. Overall, these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could facilitate the follow-up of patients with CeD. Tools identified in this work included the CeD-specific serology, dietetic questionnaires, symptomatology, and the duodenal biopsy. Review of the literature revealed that the rates of GFD adherence may vary between 30%-93% using either stool or urine GIP determination, 49%-96% by the serology, 59%-94% using the dietetic questionnaires, 56%-95% by the reported symptoms and 44%-76% with the duodenal biopsy. In addition, the association between the different methods and histological abnormalities (Marsh II-III) was found to be 33%-100% for GIP determination (stool and urine), 25%-39% for CeD-specific serology, 3%-50% for dietetic questionnaires, and 22%-28% for the symptomatology.CONCLUSIONExcreted GIP detection is the precise approach for determining voluntary or involuntary gluten consumption in CeD patients preventing future complications arising from gluten exposure.

Celiac Disease.

Celiac Disease.

Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T-Cell-Directed Therapies.

Gluten‐specific CD4+ T cells being drivers of celiac disease (CeD) are obvious targets for immunotherapy. Little is known about how cell markers harnessed for T‐cell‐directed therapy can change with time and upon activation in CeD and other autoimmune conditions. In‐depth characterization of gluten‐specific CD4+ T cells and CeD‐associated (CD38+ and CD103+) CD8+ and γδ + T cells in blood of treated CeD patients undergoing a 3 day gluten challenge is reported. The phenotypic profile of gluten‐specific cells changes profoundly with gluten exposure and the cells adopt the profile of gluten‐specific cells in untreated disease (CD147+, CD70+, programmed cell death protein 1 (PD‐1)+, inducible T‐cell costimulator (ICOS)+, CD28+, CD95+, CD38+, and CD161+), yet with some markers being unique for day 6 cells (C‐X‐C chemokine receptor type 6 (CXCR6), CD132, and CD147) and with integrin α4β7, C‐C motif chemokine receptor 9 (CCR9), and CXCR3 being expressed stably at baseline and day 6. Among gluten‐specific CD4+ T cells, 52% are CXCR5+ at baseline, perhaps indicative of germinal‐center reactions, while on day 6 all are CXCR5−. Strikingly, the phenotypic profile of gluten‐specific CD4+ T cells on day 6 largely overlaps with that of CeD‐associated (CD38+ and CD103+) CD8+ and γδ + T cells. The antigen‐induced shift in phenotype of CD4+ T cells being shared with other disease‐associated T cells is relevant for development of T‐cell‐directed therapies.

A Portable Gluten Sensor for Celiac Disease Patients May Not Always Be Reliable Depending on the Food and the User.

A strict lifelong gluten-free (GF) diet is currently the only known effective treatment for celiac disease (CD), an inflammatory disorder of the small intestine with a worldwide prevalence of about 1%. CD patients need to avoid wheat, rye, and barley and consume GF foods containing <20 mg/kg of gluten. However, strict adherence to a GF diet tends to reduce the quality of life of CD patients compared to the general population and may lead to fear of inadvertent gluten consumption, especially when eating out. To help alleviate risk of gluten exposure, a portable gluten sensor was developed by Nima Labs that allows CD patients to test foods on site prior to consumption. With very limited independent information on the analytical performance of the Nima sensor available so far, our aim was to evaluate the reliability of the sensor using a variety of different foods with defined gluten content. All samples were tested with the sensor and analyzed by enzyme-linked immunosorbent assay as reference method. Of the 119 samples with gluten content ranging from 2 to 101,888 mg/kg tested in total, the sensor showed 80 positive (67.2%), 37 negative (31.1%) and 2 invalid results at the first of three consecutive measurements. The detection rate for samples containing ≥20 mg/kg of gluten was 90%. Samples containing 2 mg/kg of gluten or below consistently tested negative, but samples with a gluten content between 2 to 20 mg/kg of gluten may either test positive or negative. Overall, the performance of the sensor was acceptable in our study, but we observed systematic variation between different users that also appeared to depend on the sample being tested. This highlights the need to improve user education especially regarding the effect of sampling, testing limitations in case of partially hydrolyzed, fractionated or fermented gluten and training users on how to perform the test in a way that gluten will be reliably detected.

Food Safety and Cross-Contamination of Gluten-Free Products: A Narrative Review.

A gluten-free diet (GFD) is currently the only effective treatment for celiac disease (CD); an individual’s daily intake of gluten should not exceed 10 mg. However, it is difficult to maintain a strict oral diet for life and at least one-third of patients with CD are exposed to gluten, despite their best efforts at dietary modifications. It has been demonstrated that both natural and certified gluten-free foods can be heavily contaminated with gluten well above the commonly accepted threshold of 20 mg/kg. Moreover, meals from food services such as restaurants, workplaces, and schools remain a significant risk for inadvertent gluten exposure. Other possible sources of gluten are non-certified oat products, numerous composite foods, medications, and cosmetics that unexpectedly contain “hidden” vital gluten, a proteinaceous by-product of wheat starch production. A number of immunochemical assays are commercially available worldwide to detect gluten. Each method has specific features, such as format, sample extraction buffers, extraction time and temperature, characteristics of the antibodies, recognition epitope, and the reference material used for calibration. Due to these differences and a lack of official reference material, the results of gluten quantitation may deviate systematically. In conclusion, incorrect gluten quantitation, improper product labeling, and poor consumer awareness, which results in the inadvertent intake of relatively high amounts of gluten, can be factors that compromise the health of patients with CD.

Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study.

Goals:This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS).Background:While gluten-induced neurocognitive impairment (GINI; eg, “celiac fog” or “brain fog”) is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences.Study:A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument.Results:The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts.Conclusions:This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.

Non-responsive celiac disease in children on a gluten free diet.

BACKGROUNDNon-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.AIMTo determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODSRetrospective cohort study performed at Boston Children’s Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTSSix hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.CONCLUSIONNRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.

Nutritional quality and costs of gluten-free products: a case-control study of food products on the Norwegian marked.

BackgroundCeliac disease is a chronic autoimmune disease triggered by gluten exposure in genetically predisposed individuals. A life-long intake of a gluten-free (GF) diet is required for its management. Wheat, rye and barley are eliminated in a GF diet and the nutritional adequacy of the diet has been questioned. In Norway, cereals and bread constitute a key role of the diet and are the main source of fiber intake. Gluten restrictions may therefore offer important implications for nutrient adequacy especially linked to fiber intake in people with celiac disease.ObjectiveThe aim of the study was to investigate the nutritional quality and price of GF products and compare with gluten-containing counterparts available at instead of in the Norwegian market.DesignThe macronutrient content of 423 unique GF products were compared with 337 equivalents with gluten. All products were selected from grocery stores and web-based shops, with the aim of including as many GF products as possible. Listed macronutrients content and price in 11 different food categories were compared to gluten-containing counterparts with Wilcoxon signed rank test.ResultsThe GF products contained less protein and fiber, and higher content of saturated fat, carbohydrate and salt compared to the gluten-containing products. The total amount of fat was not different between the groups. A similar pattern was found within several of the food categories. More gluten-containing products met the nutrition claim “high in fiber” (fiber > 6 g/100 g) compared to the GF products. The price of the GF products was higher; ranging from 46%–443% more expensive than the gluten-containing products.ConclusionGF products are less nutritious and have a higher price compared to equivalent gluten-containing products. Knowing that an unhealthy diet is the most important risk factor for developing non-communicable diseases, the nutritional quality of a GF diet needs to be addressed and should be improved.

Gluten-Free Foods Cooked in Shared Fryers With Wheat: A Pilot Study Assessing Gluten Cross Contact.

Introduction: Consumers with celiac disease are discouraged from eating fried foods cooked in shared fryers with wheat-containing foods at restaurants based on presumed gluten exposure. The purpose of the present study is to assess gluten levels of fries free of gluten-containing ingredients cooked in shared fryers with wheat.Methods: 20 orders of fries were purchased from 10 different restaurants. Restaurants confirmed that fries and oil were free of gluten-containing ingredients. All restaurants confirmed that their fryers were used to cook wheat-containing foods. Fries were sent to Bia Diagnostics and tested in 1-gram duplicates using the R7001 sandwich R5 ELISA and the R7021 competitive R5 ELISA. A microwave control also was run.Results: The sandwich ELISA found gluten in 9/20 fry orders (7 to > 80 ppm). The competitive ELISA found gluten in 3/20 fry orders (14 to > 270 ppm). In the microwave control (60-ppm gluten mixture of wheat flour and canola oil), the unheated mixture tested at a mean level of 64 ppm gluten using the sandwich ELISA and 137 ppm gluten using the competitive ELISA. The mixture heated to 190°C tested at a mean level of 55 ppm gluten using the sandwich ELISA and < 10 ppm and 16 ppm gluten using the competitive ELISA.Discussion: Based on test results, 25% of fry orders would not be considered gluten-free.Summary: Gluten cross contact may occur when gluten-free foods are cooked in shared fryers with wheat. ELISAs may underperform when analyzing for gluten that has been heated.

Circulating CD103+ γδ and CD8+ T cells are clonally shared with tissue-resident intraepithelial lymphocytes in celiac disease.

Gut intraepithelial γδ and CD8+ αβ T lymphocytes have been connected to celiac disease (CeD) pathogenesis. Based on the previous observation that activated (CD38+), gut-homing (CD103+) γδ and CD8+ αβ T cells increase in blood upon oral gluten challenge, we wanted to shed light on the pathogenic involvement of these T cells by examining the clonal relationship between cells of blood and gut during gluten exposure. Of 20 gluten-challenged CeD patients, 8 and 10 had increase in (CD38+CD103+) γδ and CD8+ αβ T cells, respectively, while 16 had increase in gluten-specific CD4+ T cells. We obtained γδ and αβ TCR sequences of >2500 single cells from blood and gut of 5 patients, before and during challenge. We observed extensive sharing between blood and gut γδ and CD8+ αβ T-cell clonotypes even prior to gluten challenge. In subjects with challenge-induced surge of γδ and/or CD8+ αβ T cells, as larger populations of cells analyzed, we observed more expanded clonotypes and clonal sharing, yet no discernible TCR similarities between expanded and/or shared clonotypes. Thus, CD4+ T cells appear to drive expansion of clonally diverse γδ or CD8+ αβ T-cell clonotypes that may not be specific for the gluten antigen.

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells

ObjectivesCoeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a...

Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa.

Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators.

Rationale for Timing of Follow-Up Visits to Assess Gluten-Free Diet in Celiac Disease Patients Based on Data Mining.

The assessment of compliance of gluten-free diet (GFD) is a keystone in the supervision of celiac disease (CD) patients. Few data are available documenting evidence-based follow-up frequency for CD patients. In this work we aim at creating a criterion for timing of clinical follow-up for CD patients using data mining. We have applied data mining to a dataset with 188 CD patients on GFD (75% of them are children below 14 years old), evaluating the presence of gluten immunogenic peptides (GIP) in stools as an adherence to diet marker. The variables considered are gender, age, years following GFD and adherence to the GFD by fecal GIP. The results identify patients on GFD for more than two years (41.5% of the patients) as more prone to poor compliance and so needing more frequent follow-up than patients with less than 2 years on GFD. This is against the usual clinical practice of following less patients on long term GFD, as they are supposed to perform better. Our results support different timing follow-up frequency taking into consideration the number of years on GFD, age and gender. Patients on long term GFD should have a more frequent monitoring as they show a higher level of gluten exposure. A gender perspective should also be considered as non-compliance is partially linked to gender in our results: Males tend to get more gluten exposure, at least in the cultural context where our study was carried out. Children tend to perform better than teenagers or adults.

Persistent Villous Atrophy in De Novo Adult Patients With Celiac Disease and Strict Control of Gluten-Free Diet Adherence: A Multicenter Prospective Study (CADER Study).

A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 μg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

Verifying Diagnosis of Refractory Celiac Disease With Urine Gluten Immunogenic Peptides as Biomarker.

Refractory celiac disease (RCD) involves T-lymphocyte activation despite supposed absence of gluten exposure. Assessing dietary adherence is the cornerstone of RCD diagnosis, but available diagnostic tools fail to monitor gluten-free diet (GFD). A recently acknowledged GFD biomarker is gluten immunogenic peptides (GIP) in urine. This study assessed urine GIP to verify whether RCD patients could be reclassified as “exposed to gluten.” Three out of four RCD patients had at least two positive-GIP urine samples in a follow-up of 3 months, demonstrating gluten exposure. Urine GIP may enable the accurate RCD verification and decrease overuse of immunosuppressants, increasing cost effectiveness.

Coeliac Disease Etiology and Pathogenesis

Coeliac disease is a chronic inflammatory autoimmune enteropathy that affects around 1% of people worldwide. It is caused by ingestion of gluten products in people who are genetically predisposed. The pathogenesis involves multifactorial factors of genetic, gluten exposure, and environmental triggers. HLA-DQ2 and HLA-DQ8 are the main responsible genes that contribute to the development of coeliac disease. Both innate and adaptive immune plays role in the pathogenesis. In this article, we will review the causes and pathogenesis of coeliac disease development.

Frontiers in Celiac Disease: Where Autoimmunity and Environment Meet.

Celiac disease is a chronic, immune-mediated enteropathy driven by dietary gluten found in genetically susceptible hosts. It has a worldwide distribution, is one of the most common autoimmune disorders globally, and is the only autoimmune condition for which the trigger is known. Despite advances in characterizing mechanisms of disease, gaps in understanding of celiac disease pathogenesis remain. A "frontier" concept is considering what moves an HLA-DQ2 or DQ8-positive individual from asymptomatic gluten tolerance to celiac disease manifestation. In this arena, environmental triggers, including age at the time of initial gluten exposure, the occurrence of usual childhood viral infections, and microbiome alterations have emerged as key events in triggering the symptomatic disease. Pathologists play a major role in frontier aspects of celiac disease. This includes the discovery that duodenal mucosal histology in follow-up biopsies does not correlate with ongoing patient symptoms, antitissue transglutaminase antibody titers and diet adherence in celiac disease patients. Further, in light of recent evidence that the detection of monoclonal T-cell populations in formalin-fixed biopsies is not specific for type II refractory celiac disease, pathologists should resist performing such analyses until common causes of "apparent" refractoriness are excluded. The promise of therapies in celiac disease has led to clinical trials targeting many steps in the inflammatory cascade, which depend upon a pathologist's confirmation of the initial diagnosis and evaluation of responses to therapies. As pathologists continue to be active participants in celiac disease research, partnering with other stakeholders, we will continue to impact this important autoimmune disease.