Melinda Ráki1, Shiva Dahal-Koirala2, Hao Yu2, Ilma R Korponay-Szabó3, Judit Gyimesi4, Gemma Castillejo5, Jørgen Jahnsen6, Shuo-Wang Qiao7, Ludvig M Sollid8. 1. Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; PreventCD Project Group. Electronic address: melinda.raki@rr-research.no. 2. Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway. 3. PreventCD Project Group; Department of Paediatrics and Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Heim Pal Children's Hospital, Budapest, Hungary. 4. PreventCD Project Group; Heim Pal Children's Hospital, Budapest, Hungary. 5. PreventCD Project Group; Paediatric Gastroenterology Unit, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Tarragona, Spain. 6. Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 7. Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway. 8. Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; PreventCD Project Group; Centre for Immune Regulation and Department of Immunology, University of Oslo, Oslo, Norway; KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
Abstract
BACKGROUND & AIMS: Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults. METHODS: We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection. RESULTS: Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes. CONCLUSIONS: T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease.
BACKGROUND & AIMS:Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults. METHODS: We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection. RESULTS: Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes. CONCLUSIONS: T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease.
Authors: Shu-Chen Hung; Tieying Hou; Wei Jiang; Nan Wang; Shuo-Wang Qiao; I-Ting Chow; Xiaodan Liu; Sjoerd H van der Burg; David M Koelle; William W Kwok; Ludvig M Sollid; Elizabeth D Mellins Journal: J Immunol Date: 2019-03-29 Impact factor: 5.422
Authors: Ludvig M Sollid; Jason A Tye-Din; Shuo-Wang Qiao; Robert P Anderson; Carmen Gianfrani; Frits Koning Journal: Immunogenetics Date: 2019-11-18 Impact factor: 2.846