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Gastroenterology. 2017 Sep;153(3):787-798.e4. doi: 10.1053/j.gastro.2017.05.016. Epub 2017 May 20.

Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes.

Author information

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.

KEYWORDS:

Autoimmunity; CD4(+) T Cell; PreventCD Study; TG2

PMID:
28535873
DOI:
10.1053/j.gastro.2017.05.016
[Indexed for MEDLINE]

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