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

Stefanolo, Juan P.; Tálamo, Martín; Dodds, Samanta; Temprano, María de la Paz; Costa, Ana F.; Moreno, María Laura; Pinto-Sanchez, M I; Smecuol, Edgardo; Vázquez, Horacio; Gonzalez, Andrea F.; Niveloni, Sonia I.; Mauriño, Eduardo; Verdú, Elena F.; Bai, Julio C.

doi:10.1016/j.cgh.2020.03.038

Cited by 55 publications

(70 citation statements)

References 17 publications

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“…Patients in the GIP+ group also showed a lower mean age at diagnosis, had a longer history of CD and had been longer on GFD than subjects negative for fecal GIPs. As was also observed in the study by Stefanolo et al [ 31 ], we found that positivity for GIPs increased with the time since diagnosis, and this may reflect a tendency to pay less attention to diet over time, especially in the case of asymptomatic subjects who begin to think they can tolerate small amounts of gluten and consequently adjust their diet.…”

Section: Discussionsupporting

confidence: 85%

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs

Porcelli

Ferretti

Biviano

et al. 2020

aog

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Background Although experts agree that strict dietary compliance is fundamental for the health of celiac patients, there are no evidence-based recommendations on the best way to assess dietary compliance. Detection of gluten immunogenic peptides (GIPs) in feces was recently proposed as an effective method of assessing the dietary compliance of celiac patients. Methods Fifty-five consecutive celiac patients (27 adults and 28 children, age 6-72 years), who had been on a gluten-free diet for at least 2 years, were enrolled. All patients were evaluated clinically for symptoms, physical parameters and laboratory parameters. Dietary compliance was assessed with the Biagi questionnaire and serum anti-tissue transglutaminase (tTG) IgA antibodies were measured. GIPs were determined by immunoenzymatic assay on an automated Chorus analyzer (DIESSE Diagnostica Senese), after extraction of fecal samples by the method developed by DIESSE. Results Eight patients tested positive for GIPs (GIPs+); 71.4% of GIP-positive patients were asymptomatic; tTG antibodies were detected in 3/8 GIP+ patients. The Biagi score was significantly associated with fecal positivity for GIPs (P=0.02). However, according to the Biagi score, 57.1% of GIP+ patients followed the diet strictly and 5.4% of GIP- subjects did not comply with the diet or made substantial mistakes. Conclusions Assay of fecal GIPs identified more patients who did not comply with the diet than did the Biagi questionnaire, evaluation of symptoms or anti-tTG antibodies. Detection of fecal GIPs offers a direct, objective, quantitative assessment of even occasional exposure to gluten and is confirmed as a practical way to check dietary compliance.

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Section: Discussionsupporting

confidence: 85%

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs

Porcelli

Ferretti

Biviano

et al. 2020

aog

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“…In our study, the main advantage of Liaison anti-tTG assay was the absence of false positives, as the two patients with positive concentrations had mucosal damage, while positive results in Quanta Flash assay were associated with lower adherence to a GFD measured by the CDAT questionnaire. In contrast, no association was observed between serum anti-tTG IgA concentrations and GIP results as also reported in previous studies [20,39], although others did find agreement between the two tests [40].…”

Section: Discussionsupporting

confidence: 63%

“…A single GIP determination displayed positive results in 22 patients (22.7%) and was associated with self-reported gluten consumption. Initial studies assessing urine or stool GIPs provided higher rates of 29.8% [ 16 ] and 46.5% [ 17 ], with positivity increasing further to between 58% to 89% when several samples were taken from the same patient over a period [ 20 , 39 ]. In these latest two studies, an increased span of testing, however, led to detecting patients with positive GIPs but no duodenal damage.…”

Section: Discussionmentioning

confidence: 99%

“…A manufacturer-sponsored study showed that 71% of the patients with Marsh type 2/3 lesions in duodenal biopsies showed negative serum antibodies, while positive urine GIPs were detected in all of the patients [ 17 ]. GIP measurement in stools, where they are present for 2–4 days after gluten ingestion, has been used to monitor adherence to GFD [ 18 , 19 , 20 ]. However, to date, no independent studies have evaluated the correlation between GIP detection in feces and changes in the duodenal mucosal histology in a real-life clinical setting.…”

Section: Introductionmentioning

confidence: 99%

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Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring

et al. 2020

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A lifelong gluten-free diet (GFD) is the only current treatment for celiac disease (CD), but strict compliance is complicated. Duodenal biopsies are the “gold standard” method for diagnosing CD, but they are not generally recommended for disease monitoring. We evaluated the sensitivity and specificity of fecal gluten immunogenic peptides (GIPs) to detect duodenal lesions in CD patients on a GFD and compared them with serum anti-tissue transglutaminase (tTG) IgA antibodies. A prospective study was conducted at two tertiary centers in Spain on a consecutive series of adolescents and adults with CD who maintained a long-lasting GFD. Adherence to a GFD and health-related quality of life were scored with validated questionnaires. Mucosal damage graded according to the Marsh–Oberhüber classification (Marsh 1/2/3) was used as the reference standard. Of the 97 patients included, 27 presented duodenal mucosal damage and 70 had normal biopsies (Marsh 0). The sensitivity (33%) and specificity (81%) of GIPs were similar to those provided by the two assays used to measure anti-tTG antibodies. Scores in questionnaires showed no association with GIP, but an association between GIPs and patients’ self-reported gluten consumption was found (p = 0.003). GIP displayed low sensitivity but acceptable specificity for the detection of mucosal damage in CD.

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“…however, unintentional gluten exposures may be more common than realised and are distinct from lapses in an otherwise intentionally strict GFD. 4,5 Compared to other chronic health conditions, the treatment burden of coeliac disease is high. 6 The limitations and socio-emotional toll of a GFD are increasingly recognised, 7 which along with high rates of ongoing symptoms and enteropathy on a GFD are driving efforts to develop adjunctive or alternative therapies to a GFD.…”

Section: Introductionmentioning

confidence: 99%

Exposure sources, amounts and time course of gluten ingestion and excretion in patients with coeliac disease on a gluten‐free diet

Silvester

Comino

Rigaux

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundA major deficit in understanding and improving treatment in coeliac disease (CD) is the lack of empiric data on real world gluten exposure.AimsTo estimate gluten exposure on a gluten‐free diet (GFD) using immunoassays for gluten immunogenic peptides (GIP) and to examine relationships among GIP detection, symptoms and suspected gluten exposuresMethodsAdults with biopsy‐confirmed CD on a GFD for 24 months were recruited from a population‐based inception cohort. Participants kept a diary and collected urine samples for 10 days and stools on days 4‐10. ‘Doggie bags’ containing ¼ portions of foods consumed were saved during the first 7 days. Gluten in food, stool and urine was quantified using A1/G12 ELISA.ResultsEighteen participants with CD (12 female; age 21‐70 years) and three participants on a gluten‐containing diet enrolled and completed the study. Twelve out of 18 CD participants had a median 2.1 mg gluten per exposure (range 0.2 to >80 mg). Most exposures were asymptomatic and unsuspected. There was high intra‐individual variability in the interval between gluten ingestion and excretion. Participants were generally unable to identify the food.ConclusionsGluten exposure on a GFD is common, intermittent, and usually silent. Excretion kinetics are highly variable among individuals. The amount of gluten varied widely, but was typically in the milligram range, which was 10‐100 times less than consumed by those on an unrestricted diet. These findings suggest that a strict GFD is difficult to attain, and specific exposures are difficult to detect due to variable time course of excretion.

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

Cited by 55 publications

References 17 publications

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs

Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring

Exposure sources, amounts and time course of gluten ingestion and excretion in patients with coeliac disease on a gluten‐free diet

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