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  • Jefferson Adams
    Jefferson Adams

    New Urine Test Can Spot Gluten in Celiac Patients

    Reviewed and edited by a celiac disease expert.

    The detection of gluten immunogenic peptides in the urine of celiac patients reveals transgressions in the gluten-free diet and incomplete mucosal healing.

    New Urine Test Can Spot Gluten in Celiac Patients - Image: CC--Retinafunk
    Caption: Image: CC--Retinafunk

    Celiac.com 06/12/2018 - A life-long gluten-free diet is the only proven treatment for celiac disease. However, current methods for assessing gluten-free diet compliance are lack the sensitivity to detect occasional dietary transgressions that may cause gut mucosal damage. So, basically, there’s currently no good way to tell if celiac patients are suffering gut damage from low-level gluten contamination.

    A team of researchers recently set out to develop a method to determine gluten intake and monitor gluten-free dietary compliance in patients with celiac disease, and to determine its correlation with mucosal damage. The research team included ML Moreno, Á Cebolla, A Muñoz-Suano, C Carrillo-Carrion, I Comino, Á Pizarro, F León, A Rodríguez-Herrera, and C Sousa. They are variously affiliated with Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain; Biomedal S.L., Sevilla, Spain; Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Celimmune, Bethesda, Maryland, USA; and the Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain.



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    For their study, the team collected urine samples from 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIPs and an LFT reader. 

    They detected GIPs in concentrated urines from healthy individuals previously subjected to gluten-free diet as early as 4-6 h after single gluten intake, and for 1-2 days afterward. The urine test showed gluten ingestion in about 50% of patients. Biopsy analysis showed that nearly 9 out of 10 celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed signs of gut damage.

    The ability to use GIP in urine to reveal gluten consumption will likely help lead to new and non-invasive methods for monitoring gluten-free diet compliance. The test is sensitive, specific and simple enough for clinical monitoring of celiac patients, as well as for basic and clinical research applications including drug development.

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    I have the celiac type that affects skin and nervous system. If I consume it my cognitive ability takes a dive as well as many other symptoms, include trouble in the bathroom. Does not show up as 'positive' in current diagnosis methods unless a hideous rash is present (skin biopsy). I'm always hoping there is active research for my type : (   This new detection method is a nice stepping stone for majority but gathering from this article I assume wouldn't suit me.

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    The idea of having a jar available (like ketone strips) for home use by those of us who were diagnosed by biopsy, follow a gluten free diet, yet still have symptoms. We could access whether or not there is hidden gluten in our diets then figure out where modifications need to be made or if there is something different going on.

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    In response to Trisha's comment, there is a home urine test for the detection of gluten consumption called Gluten Detective. However it is only sensitive to 500 mg of gluten which is 10 to 20 times more than was detectable in method used in this study. And the methodology described in the article is not feasible as a home test but maybe it will be adapted one day? As a newly diagnosed person with celiac disease I was concerned about whether I was following the diet as well as I thought I was,  so I bought and used the Gluten Detective kit for use with a stool sample - it is 10 times more sensitive than the urine kit and will detect 50 mg of inadvertent gluten ingestion in the previous several days. It is expensive for a single use test ($25) but I must say the results were very re-assuring that I had not been exposed to gluten. Around the same time I had my tTGA tested and, while still high 3 months after diagnosis and starting the gluten-free diet, my antibodies had dropped from 3600 to 150. So both those pieces of data re-assured me that I was on track to recovery. But it would be terrific to have a simple, quick & inexpensive home test kit to monitor our gluten ingestion.

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  • About Me

    Jefferson Adams

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


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  • Related Articles

    Jefferson Adams
    Celiac.com 10/13/2009 - The standard method of measuring successful observance of a gluten-free diet in patients with celiac disease is through a dietary interview performed by health professional. However, there is currently have no simple, objective method for conducting such a dietary interview.
    To address this discrepancy, a team of researchers recently designed an easy, quick questionnaire based on four simple questions which yield a five-level score (0–IV). The score provides the test individual with an indication of their compliance level.
    The research team was made up of Federico Biagi, Alida Andrealli, Paola Ilaria Bianchi, Alessandra Marchese, Catherine Klersy, and Gino Roberto Corazza.
    The team recently set out to assess the accuracy of the questionnaire. They ran the questions past 168 celiac patients, 126 females and 42 males, with a median age of 42·4 (SD 12·9) years. All subjects were allegedly following a gluten-free diet (median 82, 25th–75th percentile 50–108, range 15–389 months).
    They compared the resulting scores with the persistence of both villous atrophy and endomysial antibodies while on a gluten-free diet.  They also compared patient survival rates. Non-expert personnel interviewed patients by telephone.
    The questionnaire took less than one minute to complete. The lowest results were markedly more common among the patients with a persistence of both villous atrophy and positive endomysial antibodies. Those patients also had significantly higher rates of death overall.
    From these results, the researchers conclude that the questionnaire offers a simple, accurate way to verify compliance with a gluten-free diet for patients with celiac disease.
    Source:
    British Journal of Nutrition (2009), 102, 882–887



    Jefferson Adams
    Celiac.com 12/13/2010 - Driven by the high prevalence of celiac disease, a team of researchers based in Italy to assess a new, noninvasive disease screening strategy that would allow them to make an early diagnosis of celiac disease in 6- to 8-year-old children.
    Timely diagnosis will help doctors to initiate a gluten-free diet in willing patients, achieve growth targets, and prevent celiac disease complications.
    For the study, the research team recruited 5000 subjects, and ultimately tested 4048 saliva samples for anti-tissue transglutaminase (tTG) and immunoglobulin (Ig)A using fluid-phase radioimmunoprecipitation.
    For children with positive samples, the team arranged follow-up screening by serum radioimmunoassay tTG IgA, enzyme-linked immunosorbent assay tTG IgA, and anti-endomysium IgA. Children with positive serum assays underwent endoscopy with duodenal biopsies, and researchers advised those diagnosed with celiac disease to start a gluten-free diet.
    The team gained screening consent from 4242 parents (84.8%), and obtained usable saliva samples from a total of 4048 children (95.4%). Thirty-two children showed positive salivary tTG IgA, with another nine showing borderline autoantibody results.
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    This makes for a celiac disease rate of 1.16% in the study population, including 19 known cases of celiac disease.
    The results show that screening detected three cases of celiac disease for every two cases diagnosed before screening was 3:2. The ratio between symptomatic and asymptomatic patients was 1:1.6.
    The study shows that saliva screens for celiac disease can be  effective in identifying celiac disease early in childhood.
    Also, for this study at least, the data shows full compliance with gluten-free diet in the children diagnosed with celiac disease.
    Source:

    Journal of Pediatric Gastroenterology & Nutrition 3 November 2010. doi: 10.1097/MPG.0b013e3181e6f2d0



    Jefferson Adams
    Celiac.com 02/24/2012 - Currently, testing for anti tissue-transglutaminase antibodies is the standard of celiac disease blood testing. The test has a high sensitivity in patients who are eating a diet that contains gluten, but poor sensitivity for people on a gluten-free diet. So, it's not much use for measuring gluten-free diet success in people with celiac disease.
    A research team set out to determine if a new test might be more useful than current standard in assessing long-term gluten exposure in celiac disease patients attempting to follow a gluten-free diet. The new test measures Immunoglobulin-A antibodies to catalytically active open conformation tissue-transglutaminase.
    The study team included K. Pallav, D. A. Leffler, M. Bennett, S. Tariq, H. Xu, T. Kabbani, A. C. Moss, M. Dennis, C. P. Kelly, D. Schuppan. They are affiliated with the Celiac Center of the Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.
    The team made a preliminary dietary assessment of 147 patients with celiac disease, and grouped them according to good or poor compliance to a gluten-free diet. The team used 50 patients with inflammatory bowel disease as a control group.
    The team then measured both open (new test) and closed (conventional) tissue-transglutaminase levels using standard enzyme linked immunosorbent assay.
    The team's initial dietary review indicated that 128 of the celiac patients had followed a gluten free diet for more than six months. They found 19 to have poor compliance to a gluten-free diet.
    Of the 19 who had poor adherence to a gluten-free diet, the team found 13 patients (68.4%) who tested positive using open conformation assay (p=0.51), while ten of the 19 patients (52.6%) tested positive using conventional assay (p=0.51). In the control group, just two patients tested positive using closed assay, while one tested positive using open assay.
    The team concluded that, compared to conventional testing, open conformation tissue-transglutaminase may offer greater sensitivity in the poor gluten-free diet adherence group and higher specificity in the control population.
    The team suggests studies on larger populations to determine whether open conformation tissue-transglutaminase assay may be superior to the conventional assay in measuring compliance with a gluten-free diet.
    Source:

    Dig Liver Dis. 2012 Jan 17.


    Jefferson Adams
    Celiac.com 12/08/2016 - People with celiac disease are supposed to follow a strict lifelong gluten-free diet. Celiac patients should receive regular follow-up dietary interviews and blood tests to make sure that they are successfully following the diet.
    However, none of these methods offer an accurate measure of dietary compliance. The only way to know for sure, is to test. A team of researchers recently set out to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of gluten-free diet adherence in celiac patients and compare it with traditional methods of gluten-free diet monitoring.
    The team conducted a prospective, nonrandomized, multi-center study including 188 celiac patients on gluten-free diet and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). They simultaneously measured serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies.
    A total of 56 of the 188 celiac patients, about 30 percent, had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age. Nearly forty percent occurred in in subjects 13 years of age or older, with 60% occurring in men 13 years of age or older.
    The team found no connection between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, they did spot a connection between GIP and anti-DGP antibodies, with seven of the 53 GIP stool-positive patients testing positive for anti-DGP.
    The detection of gluten peptides in stool samples shows the limits of traditional methods for monitoring a gluten-free diet in celiac patients. The GIP ELISA provides direct and quantitative assessment of gluten exposure soon after consumption, and might improve diagnosis and clinical management of non-responsive celiac disease and refractory celiac disease.
    Basically, doctors need to take a much more hands on role in monitoring celiac patients who are following gluten-free diets.
    Source:
    Am J Gastroenterol 2016; 111:1456–1465; doi:10.1038/ajg.2016.439; published online 20 September 2016 The research team included Isabel Comino PhD1, Fernando Fernández-Bañares MD, PhD2, María Esteve MD, PhD2, Luís Ortigosa MD, PhD3, Gemma Castillejo MD, PhD4, Blanca Fambuena MS5, Carmen Ribes-Koninckx MD, PhD6, Carlos Sierra MD, PhD7, Alfonso Rodríguez-Herrera MD, PhD8, José Carlos Salazar MD9, Ángel Caunedo MD10, J M Marugán-Miguelsanz MD, PhD11, José Antonio Garrote MD, PhD12, Santiago Vivas MD, PhD13, Oreste lo Iacono MD, PhD14, Alejandro Nuñez BSc13, Luis Vaquero MD, PhD13, Ana María Vegas MD12, Laura Crespo MD12, Luis Fernández-Salazar MD, PhD11, Eduardo Arranz MD, PhD11, Victoria Alejandra Jiménez-García MD10, Marco Antonio Montes-Cano MD, PhD15, Beatriz Espín MD, PhD9, Ana Galera MD8, Justo Valverde MD8, Francisco José Girón MD7, Miguel Bolonio MSc6, Antonio Millán MD, PhD5, Francesc Martínez Cerezo 4, César Guajardo MD3, José Ramón Alberto MD3, Mercé Rosinach MD, PhD2, Verónica Segura BSc1, Francisco León MD, PhD16, Jorge Marinich PhD17, Alba Muñoz-Suano PhD17, Manuel Romero-Gómez MD, PhD5, Ángel Cebolla PhD17 and Carolina Sousa PhD1
    They are variously affiliated with the Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain; the Department of Gastroenterology, Hospital Universitari Mutua Terrassa, and CIBERehd, Terrassa, Barcelona, Spain; the Pediatric Gastroenterology, Hospital Universitario Nuestra Señora de La Candelaria, Tenerife, Spain; Pediatric Gastroenterology, Hospital Universitari de Sant Joan de Reus, IISPV, URV, Reus, Spain; the Unit for the Clinical Management of Digestive Diseases and CIBERehd and Gastroenterology and Nutrition Unit, Hospital Universitario Virgen de Valme, Seville, Spain; the Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario y Politécnico La Fe, Celiac Disease and Digestive Inmunopatology Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; the Pediatric Gastroenterology and Nutrition Unit, Hospital Materno-Infantil, Malaga, Spain; the Gastroenterology and Nutrition Unit, Instituto Hispalense de Pediatría, Seville, Spain; the Servicio de Gastroenterología Pediátrica, Hospital Universitario Virgen del Rocío, Seville, Spain; the Hospital Universitario Virgen Macarena, Seville, Spain; the Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid, CSIC and Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; the Clinical Analysis and Pediatrics, Hospital Universitario Río Hortega, Valladolid, Spain; the Servicio de Aparato Digestivo, Hospital Universitario de Leon, Leon, Spain; the Sección de Aparato Digestivo, Hospital del Tajo, Madrid, Spain; the Servicio de Inmunología, CIBER de Epidemiología y Salud Pública, Hospital Universitario Virgen del Rocío/IBiS/CSIC/Universidad de Sevilla, Seville, Spain; with Celimmune, Bethesda, Maryland, USA, and with Biomedal SL, Seville, Spain


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