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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.

Objective: Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage., Design: Urine samples of 76 healthy subjects and 58 patients with CD subjected to different gluten dietary conditions were collected. A lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant gluten immunogenic peptides (GIP) and a LFT reader were used to quantify GIP in solid-phase extracted urines., Results: GIP were detectable in concentrated urines from healthy individuals previously subjected to GFD as early as 4-6 h after single gluten intake, and remained detectable for 1-2 days. The urine assay revealed infringement of the GFD in about 50% of the patients. Analysis of duodenal biopsies revealed that most of patients with CD (89%) with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed incomplete intestinal mucosa recovery., Conclusion: GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development., Trial Registration Number: NCT02344758., Competing Interests: Competing interests: ÁC and FL own stock in Biomedal SL. Other authors have declared no conflict of interest. The method of this manuscript was included in a patent application by MLM, CS, AR-H and ÁC as inventors with the assigned number P201400569., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Gluten-free diet (GFD) is the only treatment for celiac disease (CD). There is a general consensus that strict GFD adherence in CD patients leads to full clinical and histological remission accompanied by improvement in quality of life and reduced long-term complications. Despite the importance of monitoring the GFD, there are no clear guidelines for assessing the outcome or for exploring its adherence. Available methods are insufficiently accurate to identify occasional gluten exposure that may cause intestinal mucosal damage. Serological tests are highly sensitive and specific for diagnosis, but do not predict recovery and are not useful for follow-up. The use of serial endoscopies, it is invasive and impractical for frequent monitoring, and dietary interview can be subjective. Therefore, the detection of gluten immunogenic peptides (GIP) in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients. These simple immunoassays in human samples could overcome some key unresolved scientific and clinical problems in CD management. It is a significant advance that opens up new possibilities for the clinicians to evaluate the CD treatment, GFD compliance, and improvement in the quality of life of CD patients., Competing Interests: The authors declare no conflict of interest.

Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring., Methods: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously., Results: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP., Conclusions: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397., Competing Interests: Guarantor of the article: Carolina Sousa, PhD. Specific author contributions: Study concept and design: I.C., F.F.-B., M.E., L.O., G.C., B.F., C.R.K., C.S., A.R.-H., J.C.S., Á.C., J.M.M.M., J.A.G., S.V., O.L.I., A.N., L.V., A.M.V., L.C., L.F.-S., E.A., V.A.J.G., M.A.M.-C., B.E., A.G., J.V., F.J.G., M.B., A.M., C.G., J.R.A., M.R., M.R.-G., V.S., F.L., J.M., A.M.S., Á.C. and C.S.; acquisition of data: I.C., V.S., F.L., A.M.S., Á.C. and C.S.; analysis and interpretation of data: I.C., V.S., F.L., A.M.S., Á.C. and C.S.; technical and material support: I.C., V.S., F.L., A.M.S., Á.C. and C.S.; drafting of the manuscript: I.C., Á.C. and C.S.; critical revision of the manuscript and important intellectual content: I.C., F.F.-B., M.E., L.O., G.C., B.F., C.R.K., C.S., A.R.-H., J.C.S., A.C., J.M.M.M., J.A.G., S.V., O.L.I., A.N., L.V., A.M.V., L.C., L.F.-S., E.A., V.A.J.G., M.A.M.-C., B.E., A.G., J.V., F.J.G., M.B., A.M., C.G., J.R.A., M.R., M.R.-G., V.S., F.L., J.M., A.M.S., Á.C. and C.S. Financial support: This work was supported by grants from Ministerio de Ciencia e Innovación and FEDER funds (DELIAC, IPT-2011-0952-900000), and Corporación Tecnológica de Andalucía (SINGLUCHECK, 1737/0118). We also thank the generous volunteer subjects who enrolled in the study. Potential competing interests: Á.C. and F.L. own stock in Biomedal SL. Other authors declare no conflict of interest.

Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available., Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces., Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody., Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients., Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867.

Background The treatment of celiac disease (CD) is a lifelong gluten-free diet (GFD). The current methods for monitoring GFD conformance, such as a dietary questionnaire or serology tests, may be inaccurate in detecting dietary transgressions, and duodenal biopsies are invasive, expensive, and not a routine monitoring technique. Objectives Our aim was to determine the clinical usefulness of urine gluten immunogenic peptides (GIP) as a biomarker monitoring GFD adherence in celiac patients and to evaluate the concordance of the results with the degree of mucosal damage. Methods A prospective observational study was conducted involving 22 de novo CD patients, 77 celiac patients consuming a GFD, and 13 nonceliac subjects. On 3 d of the week, urine samples were collected and the GIP concentrations were tested. Simultaneously, anti-tissue transglutaminase antibodies, questionnaire results, clinical manifestations, and histological findings were analyzed. Results Approximately 24% (18 of 76) of the celiac patients consuming a GFD exhibited Marsh II–III mucosal damage. Among this population, 94% (17 of 18) had detectable urine GIP; however, between 60% and 80% were asymptomatic and exhibited negative serology and appropriate GFD adherence based on the questionnaire. In contrast, 97% (31 of 32) of the celiac patients without duodenal damage had no detectable GIP. These results demonstrated the high sensitivity (94%) and negative predictive value (97%) of GIP measurements in relation to duodenal biopsy findings. In the de novo CD-diagnosed cohort, 82% (18 of 22) of patients had measurable amounts of GIP in the urine. Conclusions Determining GIP concentrations in several urine samples may be an especially convenient approach to assess recent gluten exposure in celiac patients and appears to accurately predict the absence of histological lesions. The introduction of GIP testing as an assessment technique for GFD adherence may help in ascertaining dietary compliance and to target the most suitable intervention during follow-up. [ABSTRACT FROM AUTHOR]