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Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 08/28/2017 - After 14-day gluten challenge, an HLA-DQ-gluten tetramer blood test provides better detection of celiac disease than biopsy. Can that lead to new disease detection methods in patients who are already on a gluten-free diet? Doctors attempting to diagnose celiac disease are often confronted by patients who have already given up gluten. For such patients, diagnostic guidelines currently call for a gluten challenge of at least 14 days, followed by duodenal biopsy. There isn't much good data on how many false-positive results are generated by this method. To get a better picture, a team of researchers recently studied responses to 14-day gluten challenge in subjects with treated celiac disease. The research team included Vikas K Sarna, Gry I Skodje, Henrik M Reims, Louise F Risnes, Shiva Dahal-Koirala, Ludvig M Sollid, and Knut E A Lundin. They are variously affiliated with the Department of Immunology and Transfusion Medicine, Oslo University Hospital, Norway; K. G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway; Department of Clinical Service, Oslo University Hospital, Norway; Department of Pathology, Oslo University Hospital, Norway; Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Norway; and the Department of Gastroenterology, Oslo University Hospital, Norway. The research team took a group of 20 patients with biopsy-verified celiac disease, all in confirmed mucosal remission, and presented them with a dietary gluten challenge of 5.7 grams per oral gluten per day for 14 days, then conducted duodenal biopsies. They analyzed blood by multiplex assay for cytokine detection, and by flow cytometry using HLA-DQ:gluten tetramers. Nineteen of the twenty participants completed the challenge. Biopsy results showed villous blunting in 5 of those 19 patients. Villous height to crypt depth ratio reduced with at least 0.4 concomitantly with an increase in intraepithelial lymphocyte count of at least 50% in 9 of the 19 patients. Interleukin-8 plasma concentration increased by more than 100% after 4 hours in 7 of 19 subjects. Frequency of blood CD4+effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells increased by more than 100% on day 6 in 12 of 15 evaluated participants. For most celiac patients, a 14-day gluten challenge did not result in sufficient mucosal architectural changes for clear diagnosis (sensitivity ≈25%–50%). The team found that an increase in CD4+ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells in blood 6 days after gluten challenge is a more sensitive and less invasive biomarker for celiac disease. The team is calling for further study. Being able to diagnose celiac disease without biopsy could really help to improve the entire diagnostic process, and could easily lead to an increase in diagnosis. Source: Gut
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 04/18/2011 - In an effort to improve diagnosis of celiac disease in patients already on a gluten-free diet, a team of researchers recently evaluated HLA-DQ2-gliadin tetramers for detection of gluten-specific T cells in peripheral blood and histological changes in the duodenum after a short gluten challenge as a diagnostic tool. The study team included Margit Brottveit MD, Melinda Ráki MD, PhD, Elin Bergseng MScPharm, PhD, Lars-Egil Fallang MSc, PhD, Bjørg Simonsen BLS, Astrid Løvik MSc, Stig Larsen MSc, PhD, Else Marit Løberg MD, PhD, Frode L Jahnsen MD, PhD, Ludvig M Sollid MD, PhD, and Knut EA Lundin MD, PhD. They are associated variously with the Department of Gastroenterology, the Department of Medicine, and the Department of Pathology at Oslo University Hospital in Ullevål, Norway, the Centre for Immune Regulation at the Institute of Immunology at the University of Oslo and Oslo University Hospital, the Department of Pathology at Oslo University Hospital in Rikshospitalet, Norway, and the Norwegian School of Veterinary Medicine, Oslo, Norway. For their study, the team evaluated HLA-DQ2+ individuals on a gluten-free diet for at least 4 weeks. 35 patients had uncertain diagnosis, 13 patients had celiac disease, and 2 healthy subjects served as disease controls. The team challenged each participant with four slices of gluten-containing white bread per day for 3 days (d1–d3). The team took biopsy samples via esophagogastroduodenoscopy on d0 and d4, and scored the biopsies using Marsh criteria. On d0 and d4, team isolated peripheral blood celiac disease 4+ T cells, stained them with HLA-DQ2-gliadin peptide tetramers, and analyzed the results using flow cytometry. After the gluten challenge, 11 of the 13 celiac disease patients showed a positive tetramer test, while four of them also showed typical histological changes on biopsy. Of the 35 patients with uncertain celiac diagnosis, 3 were found to have celiac disease. Two of these three patients showed both positive tetramer stains and histological changes in biopsies after gluten challenge. Overall, the team found celiac disease in about ten percent of the group with self-prescribed gluten-free diet. From these results, the team concluded that tetramer staining for gluten-specific T cells is a sensitive method in detecting an immune response in celiac disease patients after a short gluten challenge. SOURCE: Am J Gastroenterol advance online publication 1 March 2011; doi: 10.1038/ajg.2011.23
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 04/23/2010 - HLA-DQ2+ patients already following a gluten free diet, but with no clinical diagnosis of celiac disease, can present doctors with some challenges in making an official diagnosis of celiac disease. Because many of these patients are reluctant to endure a prolonged gluten challenge, determining whether patients have clinical celiac disease, rather than clinical gluten intolerance, can be difficult. Using HLA-DQ2-gliadin tetramers for detection of gluten specific T cells after a short gluten challenge could offer advantages in such cases. A team of researchers affiliated with the South-Eastern Norway Regional Health Authority and the University of Oslo is conducting a clinical trial to evaluate the use of HLA-DQ2-gliadin tetramer for diagnosing celiac disease. Their study will assess the use of HLA-DQ2-gliadin tetramer for staining gluten specific T cells to effectively diagnose uncertain celiac disease. The researchers hope this method will allow them to distinguish between true celiac disease and clinical gluten intolerance without celiac disease, in HLA-DQ2+ patients already on a gluten free diet, but without a clinical diagnosis of celiac disease. The study began in September 2006. The first part of the study will assess HLA-DQ2-tetramer response after gluten challenge, followed by FACS analysis of peripheral blood after gluten challenge. Final data collection for the first phase was completed in December 2009. The second part of the study is currently underway, and will assess mucosal responses to a 3 day gluten challenge. Biopsies will be conducted on the fourth day of gluten challenge. To clinically diagnose celiac disease, the researchers will take small bowel biopsies both before and after the gluten challenge, and blood samples will be taken for tetramer staining of gluten specific T cells. The second stage study group consists of 50 HLA-DQ2+ patients on a gluten free diet, both celiacs and uncertain celiacs. Subjects will face an oral gluten challenge of four slices of bread daily for three days. Pre-challenge blood samples will be drawn for tetramer staining of gluten-specific T-cells. The Institute of Immunology at Rikshospitalet, will use FACS analysis to conduct the analysis. Researchers will examine biopsies of the small intestine for morphological changes and inflammatory gene expression. They will repeat these same blood sample and biopsy procedures after the gluten challenge. Registration for clinical symptoms and personality traits will be done by standardized and validated forms. A dietitian will interview all patients. The full study involves a total of100 subjects, and will be completed around December 2010. Source: ClinicalTrials.gov - ClinicalTrials.gov Identifier: NCT01100099