Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples.

BACKGROUND & AIMS: It is not clear how often patients who are on gluten-free diets (GFDs) for treatment of celiac disease still are exposed to gluten. We studied levels of gluten immunogenic peptides (GIP) in fecal and urine samples, collected over 4 weeks, from patients with celiac disease on a long-term GFD. METHODS: We performed a prospective study of 53 adults with celiac disease who had been on a GFD for more than 2 years (median duration, 8 y; interquartile range, 5-12 y) in Argentina. At baseline, symptoms were assessed by the celiac symptom index questionnaire. Patients collected stool each Friday and Saturday and urine samples each Sunday for 4 weeks. We used a commercial enzyme-linked immunosorbent assay to measure GIP in stool and point-of-care tests to measure GIP in urine samples. RESULTS: Overall, 159 of 420 stool and urine samples (37.9%) were positive for GIP; 88.7% of patients had at least 1 fecal or urine sample that was positive for GIP (median, 3 excretions). On weekends (urine samples), 69.8% of patients excreted GIP at least once, compared with 62.3% during weekdays (stool). The number of patients with a sample that was positive for GIP increased over the 4-week study period (urine samples in week 1 vs week 4: P < .05). Patients with symptoms had more weeks in which GIP was detected in stool than patients without symptoms (P < .05). The number of samples that were positive for GIP correlated with titers of deamidated gliadin peptide IgA in patients' blood samples, but not with levels of tissue transglutaminase. CONCLUSIONS: Patients with celiac disease on a long-term GFD still frequently are exposed to gluten. Assays to detect GIP in stool and urine might be used to assist dietitians in assessment of GFD compliance.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.

Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease.

Celiac disease (CeD) is a common immune-mediated disease of the small intestine that is triggered by exposure to dietary gluten. While the HLA locus plays a major role in disease susceptibility, 39 non-HLA loci were also identified in a study of 24,269 individuals. We now build on this earlier study by adding 4125 additional Caucasian samples including an Argentinian cohort. In doing so, we not only confirm the previous associations, we also identify two novel independent genome-wide significant associations at loci: 12p13.31 and 22q13.1. By applying a genomics approach and differential expression analysis in CeD intestinal biopsies, we prioritize potential causal genes at these novel loci, including LTBR, CYTH4, and RAC2. Nineteen prioritized causal genes are overlapping known drug targets. Pathway enrichment analysis and expression of these genes in CeD biopsies suggest that they have roles in regulating multiple pathways such as the tumor necrosis factor (TNF) mediated signaling pathway and positive regulation of I-κB kinase/NF-κB signaling.

Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients.

BACKGROUND: Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established. AIM: To assess the performance of enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (PoCTs) for GIP excretion in CeD patients on gluten-free diet (GFD). METHODS: We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion (by ELISA in stool and PoCTs (commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period. RESULTS: Forty-four patients were enrolled, of which 19 (43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected. Eleven out of 44 patients (25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases (Cohen´s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant (concomitantly positive or negative) in 67 out of 74 (90.5%) samples. Excretion of GIP was detected in 7 (8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports. CONCLUSION: GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple home-based method for self-assessment of dietary indiscretions.

Prevalencia de diabetes mellitus y glucemia en ayuno alterada al momento del diagnóstico de cáncer de páncreas, en un grupo de pacientes asistidos en un centro de referencia gastroenterológico en Argentina / Prevalence of diabetes mellitus and altered fasting blood glucose at the time of pancreatic cancer diagnosis, in a group of patients assisted in a gastroenterological referral center in Argentina

Introducción: la diabetes mellitus (DM) se considera un factor de riesgo para el desarrollo de adenocarcinoma ductal de páncreas (ACDP). Objetivos: describir la prevalencia de DM y glucemia en ayuno alterada (GAA) al diagnóstico de ACDP en pacientes asistidos en un centro de referencia gastroenterológico; analizar las diferencias en las características personales y nutricionales en pacientes con ACDP y DM, ACDP y GAA, y ACDP sin DM ni GAA; establecer el tiempo transcurrido desde el diagnóstico de DM hasta diagnosticar ACDP. Materiales y métodos: de octubre de 2019 a marzo de 2020 se revisaron 465 historias clínicas de las Secciones Oncología y Nutrición de pacientes >18 años con diagnóstico de ACDP. Resultados: se registraron 171 historias clínicas (36,7%) con ACDP y DM, y 294 (63,2%) con ACDP sin DM. En el 45,1% de las primeras, el intervalo entre el diagnóstico de DM y el de ACDP fue <1 año, y en el 17,65%, 15,69% y 21,57% los lapsos correspondieron a 1 y 5 años, entre 5 y 10 años y >10 años respectivamente. Conclusiones: la prevalencia de DM en ACDP fue superior a la registrada en la población general (37% vs 12,7%), siendo del 45,10% cuando se presentó dentro del primer año del diagnóstico oncológico. Nuestros resultados concuerdan con la bibliografía internacional que relaciona la DM de reciente diagnóstico como factor asociado a la presencia de ACDP por factores de riesgo compartidos, variables fisiopatológicas de la DM o a consecuencia de la terapéutica farmacológica de la misma.

Introduction: diabetes mellitus (DM) is considered to be a risk factor for the development of pancreatic ductal adenocarcinoma (PDAC). Objectives: describe the prevalence of DM and of impaired fasting glucose (IFG) at the diagnosis of PDAC, among patients assisted in a gastroenterological reference center. Analyze differences in personal and nutritional characteristics in patients with both PDAC and DM; with both PDAC and IFG; and with PDAC but neither DM nor IFG. Determine the time lapse between the diagnosis of DM and the diagnosis of PDAC. Materials and methods: between October 2019 and March 2020, we analyzed 465 clinical records of PDAC-diagnosed patients over 18 years, from Oncology and Nutrition Sections. Results: 171 clinical records (36.7%) showed both PDAC and DM; 294 clinical records (63.2%) showed PDAC but not DM. In 45.1% of the former, the interval between the diagnosis of DM and that of PDAC was <1 year, and in 17.65%, 15.69% and 21.57%, the lapses corresponded to 1 and 5 years, between 5 and 10 years y >10 years, respectively. Conclusions: the prevalence of DM in PDAC patients (37%) is higher than that registered in the overall population (12.7%), reaching a 45.10% when detected during the first year of oncological diagnosis. Our results match the international literature relating recently-diagnosed DM with the presence of PDAC, as effect of shared risk factors between both diseases, or DM pathophysiology factors, or DM pharmacological therapeutic