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Celiac.com 08/20/2015 - Celiac disease is frequently mis-diagnosed. Even when patients received endoscopy, celiac disease is often missed or not detected. A team of researchers recently assessed the accuracy of finger prick-based point-of-care tests in the detection of celiac disease, and developed an algorithm for diagnosis. The research team included PD Mooney, SH Wong, AJ Johnston, M Kurien, A Avgerinos, and DS Sanders. They are variously affiliated with the Royal Hallamshire Hospital, Sheffield, United Kingdom and the University of Sheffield, Sheffield, United Kingdom. Their team conducted a prospective study of two groups of celiac disease patients evaluated at the Royal Hallamshire Hospital in Sheffield UK from March 2013 through February 2014. In group one, the team evaluated 55 patients at high risk for celiac disease, and who tested positive for endomysial antibody, using the Biocard test (BHR Pharmaceuticals, Nuneaton, UK) and the Celiac Quick Test (Biohit Healthcare UK, Ellesmere Port, UK), which measure antibodies to tissue transglutaminase (anti-tTG), and the Simtomax test (Tillotts Pharma, Rheinfelden, Switzerland), which measures deamidated gliadin peptide antibodies (DGP). Group 2 included 508 consecutive patients who received an endoscopy for any reason, received the DGP test, and also were evaluated using a diagnostic algorithm that incorporated results from the DGP test and data on symptoms. For both groups, point-of-care tests were administered at the time of endoscopy, and the results compared against results from histologic analyses of duodenal biopsy specimens from all patients. In group 1, the DGP test identified patients with celiac disease with 94.4% sensitivity, the Celiac Quick Test identified patients with 77.8% sensitivity (P = .03 vs the DGP test), while the Biocard test identified patients with 72.2% sensitivity (P = .008 vs the DGP test). In group 2, the DGP test identified patients with celiac disease with 92.7% sensitivity (95% confidence interval, 83.0-97.3), 85.2% specificity (95% confidence interval, 81.5-88.3), a positive predictive value of 49.2% (95% confidence interval, 40.3-58.2), and a negative predictive value of 98.7% (95% confidence interval, 96.8-99.5). Measurement of serum anti-tTG identified patients with celiac disease with 91.2% sensitivity (95% confidence interval, 81.1-96.4), 87.5% specificity (95% confidence interval, 84.0-90.4), a positive predictive value of 53.0% (95% confidence interval, 43.6-62.2), and a negative predictive value of 98.5% (95% confidence interval, 96.5-99.4). The algorithm identified patients with celiac disease with 98.5% sensitivity, and has the potential to reduce duodenal biopsies by 35%. In this prospective study, the test for DGP identified celiac patients with comparable sensitivity and specificity as standard serologic analysis of anti-tTG. Conducting the DGP test before endoscopy might increase the accuracy of the diagnosis of celiac disease. These results look promising, but further study is needed, in lower-prevalence populations, to more accurately determine the potential benefits of the DGP test in celiac screening. Source: Clin Gastroenterol Hepatol. 2015 Jul;13(7):1278-1284.e1. doi: 10.1016/j.cgh.2015.01.010. Epub 2015 Jan 26.
Can Testing for Antibodies to Deamidated Gliadin Peptide Allow Earlier Celiac Disease Diagnosis in Children?
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 01/29/2015 - Testing for tissue transglutaminase antibodies (TGA) is currently a common part of attempting to diagnose celiac disease. A research team wanted to find out if determination of antibodies to synthetic deamidatedgliadin peptides (anti-DGP) might work as an alternative or complement to TGA testing. To find out, the team assessed the performance of a time-resolved immunofluorometry (TR-IFMA) based anti-DGP assay in the diagnosis of celiac disease in children, and also retrospectively analyzed the appearance of anti-DGP antibodies before TGA seroconversion. The research team included A. Lammi, P. Arikoski, S. Simell, T. Kinnunen, V. Simell, S. Paavanen-Huhtala, A. Hinkkanen, R. Veijola, M. Knip, J. Toppari, O. Vaarala, O. Simell, and J. Ilonen. They are variously affiliated with the Department of Clinical Microbiology and the A.I. Virtanen Institute for Molecular Sciences at the University of Eastern Finland in Kuopio, Finland, the Department of Pediatrics at Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland, the Department of Pediatrics at the University of Oulu and Oulu University Hospital in Oulu, Finland, the Children's Hospital, and the Institute of Clinical Medicine at the University of Helsinki in Helsinki, Finland, the Folkhälsan Research Center in Helsinki, Finland, the Department of Pediatrics at Tampere University Hospital in Tampere, Finland, the Immunogenetics Laboratory, and the Department of Physiology at the University of Turku, and with the Department of Pediatrics and Adolescent Medicine at the University of Turku and Turku University Hospital in Turku, Finland. For their study, the team assessed 92 children with biopsy-confirmed celiac disease. The team took blood samples at the time of, or just prior to, clinical diagnosis. The team also assessed a control group of 82 TGA-negative children who were positive for HLA-DQ2 or -DQ8. Based on receiver operating characteristics (ROC) curves, they found that the optimal cut-off value for IgA anti-DGP positivity was 153 arbitrary units (AU) with a sensitivity of 92.4% and specificity of 97.6%, while the optimal cut-off value for IgG anti-DGP 119 AU, with a sensitivity of 97.8% and specificity of 97.6%. They found that all 92 children with celiac disease tested positive for either IgA or IgG anti-DGP at the time of diagnosis. Blood results from 48 children with celiac disease, analyzed retrospectively before the diagnosis, showed that anti-DGP antibodies preceded TGA positivity in 35 of 48 celiac disease children and appeared an average of one year earlier. From these results, the TR-IFMA test for detecting anti-DGP antibodies shows high sensitivity and specificity for celiac disease in children. For most of the patients, anti-DGP seropositivity preceded TGA positivity, which means that monitoring anti-DGP antibodies frequently in genetically susceptible children might allow doctors to spot celiac disease earlier than allowed by current tests. Source: J Pediatr Gastroenterol Nutr. 2014 Dec 16.
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 06/10/2013 - Researchers have known for some time that immunoglobulin G antibodies against deamidated gliadin peptides are about as accurate as tissue transglutaminase and endomysium autoantibodies in diagnosing celiac disease in adults. However, not much is known about their predictive value in infants with a suspected gluten enteropathy. A team of researchers recently set out to determine if antibodies to deamidated gliadin peptides could be an accurate predictor of celiac disease in infants. The research team included S. Amarri, P. Alvisi, R. De Giorgio, M.C. Gelli, R. Cicola, F. Tovoli, R. Sassatelli, G. Caio, and U. Volta. They are affiliated with the Pediatric Unit, IRCCS - Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. To test whether deamidated gliadin immunoglobulin G antibodies are more reliable than traditional tests for screening celiac disease in infants, the researchers tested 65 children under 2 years of age for deamidated gliadin immunoglobulin G, tissue transglutaminase and endomysium immunoglobulin A, and gliadin immunoglobulins A and G. The group included 42 infants with malabsorption, along with 23 infants as control subjects. Thirty-seven of the 42 children with malabsorption had deamidated gliadin antibodies, associated with tissue transglutaminase and endomysial antibodies in 33, and with gliadin immunoglobulins A and G in 21 and 29, respectively. The team conducted intestinal biopsy in 34 of the 37 children who tested positive for deamidated gliadin antibodies. Thirty-two of the 34 showed villous atrophy consistent with celiac disease, while one of the remaining two had a Marsh 1 and the other showed normal mucosa. The control group showed only gliadin immunoglobulins A (4.3 %) and G (39.1 %). The results showed that deamidated gliadin, tissue transglutaminase and endomysial antibodies were significantly more sensitive for celiac disease than gliadin immunoglobulins G and A. High levels of deamidated gliadin antibodies correlated with severe intestinal damage. For infants, deamidated gliadin antibodies showed a higher diagnostic accuracy for celiac disease than gliadin antibodies. High levels of deamidated gliadin antibodies are good predictors of severe gluten-dependent duodenal damage. Source: J Clin Immunol. 2013 Apr 5.
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 10/20/2010 - U.S. doctors and patients looking for accurate early diagnosis of celiac disease now have a state of the art celiac disease assay with a high level of sensitivity and specificity. The US Food and Drug Administration (FDA) has given 510(k) clearance for the first two fully automated gliadin tests featuring deamidated peptides for celiac disease. Manufactured by Phadia US, the tests, EliA GliadinDP IgA and EliA GliadinDP IgG, are designed to be used in conjunct with other laboratory and clinical findings in the early diagnosis of celiac disease. According to Gabi Gross, autoimmune franchise leader for Phadia US, "EliA GliadinDP IgA and EliA GliadinDP IgG will offer physicians who suspect a possible case of celiac disease, antibody tests with the lowest number of false positive results." This means less "unnecessary endoscopies and biopsies," she adds. EliA GliadinDP IgA and EliA GliadinDP IgG will offer antibody tests with the lowest number of false positive results for doctors who suspect a patient has celiac disease. The assays are optional on Laboratory Systems Phadia 100Ð„ and Phadia 250 instruments with features like quick turnaround, monthly calibration, onboard instrument dilution, and a discrete single-well, random-access, nonmicrotiter plate format. Phadia also manufactures other approved CLIA moderately complex assays in the EliA autoimmune product line, including anticardiolipin IgG/IgM, anti-B2-glycoprotein 1 IgG/IgM, cyclic citrullinated peptide, tissue transglutaminase IgA/ IgG, gliadin IgA/IgG, dsDNA, antinuclear antibody screen, and ENA antibodies to the following antigens: Sm, U1RNP, RNP70, Ro, La, Scl-70, CENP, and Jo-1. Source: Medscape
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 10/01/2009 - Antibodies to deamidated gliadin offer a promising new tool in the diagnosis of celiac disease. A team of researchers recently set out of examine serodiagnosis of childhood celiac disease assay of antibodies against deamidated gliadin. The research team was made up of Christian Prause, Thomas Richter, Sibylle Koletzko, H. Holm Uhlig, Almuthe C. Hauer, Martin Stern, Klaus-Peter Zimmer, Martin W. Laass, Christian Probst, Wolfgang Schlumberger, and Thomas Mothes. Their results show that the ELISA for gauging IgG antibodies to deamidated gliadin-analogous fusion peptides (GAF3X) performs better in children than does the ELISA for gauging antibodies against native gliadin, and compares favorably to results for IgA antibodies against tissue transglutaminase (IgA-anti-tTG). By combining investigations of IgG antibodies to GAF3X (IgG-anti-GAF3X) with IgA-anti-tTG, a significantly higher number of children were positively confirmed to have celiac disease, or to be free of celiac disease. The new IgG-anti-GAF3X ELISA detected three instances of IgA deficienc, along with two cases of silent celiac disease, in addition to improving diagnosis of children under 2 years of age. It will be interesting to see where these enhanced approaches for diagnosing celiac disease will take us. Much research certainly supports the benefits of early diagnosis and treatment, especially with respect to the development of conditions associated with untreated and/or latent celiac disease. Even the ability to diagnose a new category of gluten intolerant individuals might gain steam from more refined screening techniques. Source: Annals of the New York Academy of Sciences - Volume 1173 Issue Contemporary Challenges in Autoimmunity, Pages 28 - 35