PMID- 25083284 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140801 LR - 20211021 IS - 2050-6406 (Print) IS - 2050-6414 (Electronic) IS - 2050-6406 (Linking) VI - 2 IP - 4 DP - 2014 Aug TI - Tetramer-visualized gluten-specific CD4+ T cells in blood as a potential diagnostic marker for coeliac disease without oral gluten challenge. PG - 268-78 LID - 10.1177/2050640614540154 [doi] AB - BACKGROUND: Diagnosing coeliac disease (CD) can be challenging, despite highly specific autoantibodies and typical mucosal changes in the small intestine. The T-cell response to gluten is a hallmark of the disease that has been hitherto unexploited in clinical work-up. OBJECTIVES: We aimed to develop a new method that directly visualizes and characterizes gluten-reactive CD4+ T cells in blood, independently of gluten challenge, and to explore its diagnostic potential. METHODS: We performed bead-enrichment of DQ2.5-glia-alpha1a and DQ2.5-glia-alpha2 tetramer+ cells in the blood of control individuals, treated (TCD) and untreated patients (UCD). We visualized these cells by flow cytometry, sorted them and cloned them. We assessed their specificity by antigen stimulation and re-staining with tetramers. RESULTS: We detected significantly more gliadin-tetramer+ CD4+ effector memory T cells (TEM) in UCD and TCD patients, compared to controls. Significantly more gliadin-tetramer+ TEM in the CD patients than in controls expressed the gut-homing marker integrin-beta7. CONCLUSION: Quantification of gut-homing, gluten-specific TEM in peripheral blood, visualized with human leukocyte antigen (HLA) -tetramers, may be used to distinguish CD patients from healthy individuals. Easy access to gluten-reactive blood T cells from diseased and healthy individuals may lead to new insights on the disease-driving CD4+ T cells in CD. FAU - Christophersen, Asbjorn AU - Christophersen A AD - Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway. FAU - Raki, Melinda AU - Raki M AD - Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway. FAU - Bergseng, Elin AU - Bergseng E AD - Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway. FAU - Lundin, Knut Ea AU - Lundin KE AD - Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway ; Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital - Rikshospitalet, Oslo, Norway. FAU - Jahnsen, Jorgen AU - Jahnsen J AD - Department of Gastroenterology, Oslo University Hospital - Ulleval, Oslo, Norway. FAU - Sollid, Ludvig M AU - Sollid LM AD - Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway. FAU - Qiao, Shuo-Wang AU - Qiao SW AD - Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway. LA - eng PT - Journal Article PL - England TA - United European Gastroenterol J JT - United European gastroenterology journal JID - 101606807 EIN - United European Gastroenterol J. 2014 Dec;2(6):550. PMID: 25761984 PMC - PMC4114117 OTO - NOTNLM OT - Blood test OT - T cells OT - celiac disease OT - diagnostic marker OT - diagnostics OT - gliadin OT - gluten OT - gluten reactivity OT - histology OT - human leukocyte antigen OT - immunology EDAT- 2014/08/02 06:00 MHDA- 2014/08/02 06:01 PMCR- 2014/08/01 CRDT- 2014/08/02 06:00 PHST- 2014/02/19 00:00 [received] PHST- 2014/04/22 00:00 [revised] PHST- 2014/05/22 00:00 [accepted] PHST- 2014/08/02 06:00 [entrez] PHST- 2014/08/02 06:00 [pubmed] PHST- 2014/08/02 06:01 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - 10.1177_2050640614540154 [pii] AID - 10.1177/2050640614540154 [doi] PST - ppublish SO - United European Gastroenterol J. 2014 Aug;2(4):268-78. doi: 10.1177/2050640614540154.