Cristin-resultat-ID: 438765
Sist endret: 21. januar 2015 15:27
Resultat
Vitenskapelig artikkel
2001

Genes and environment in celiac disease

Bidragsytere:
  • Ludvig Magne Sollid
  • Stephen N. McAdam
  • Øyvind Molberg
  • Hanne Quarsten
  • Eva Helene Arentz-Hansen
  • A. S. Louka
  • mfl.

Tidsskrift

Acta Odontologica Scandinavica
ISSN 0001-6357
e-ISSN 1502-3850
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2001
Volum: 59
Sider: 189 - 196

Importkilder

ForskDok-ID: 64322

Beskrivelse Beskrivelse

Tittel

Genes and environment in celiac disease

Sammendrag

Celiac disease is an intestinal disorder that develops as a result of interplay between genetic and environmental factors. HLA genes along with non-HLA genes predispose to the disease. Linkage studies have failed to identify chromosomal regions other than the HLA region which have major effects, indicating the existence of multiple non-HLA predisposing genes with modest effects. Association studies have shown that CTLA4 or a closely located gene is one of these genes. The primary HLA association in the majority of celiac disease patients is with DQ2 (DQA1*05/DQB1*02) and in the minority of patients with DQ8 (DQA1*0301/DQB1*0302). Gluten reactive CD4+ T cells can be isolated from small intestinal biopsies of celiac patients but not from controls. DQ2 or DQ8, but not other HLA molecules carried by patients, present peptides to these T cells. A number of distinct T cell gluten epitopes exist, most of them posttranslationally modified by deamidation. DQ2 and DQ8 bind the epitopes such that the glutamic acid residues created by deamidation are accommodated in pockets that have a preference for negatively charged side chains. There is evidence that deamidation in vivo is mediated by the enzyme tissue transglutaminase (tTG). Overall, the results point to control of the immune response to gluten by intestinal T cells restricted by the DQ2 or DQ8 molecules. This is likely to be a critical checkpoint for the development of celiac disease and could explain the dominant genetic role of HLA in this disorder. The products of the other predisposing genes may participate in pathway(s) that lead(s) to lesion formation. The minor genetic effects of the non-HLA genes could indicate a lack of critical checkpoints along these pathways, or that there are several pathways leading to the lesion formation.

Bidragsytere

Ludvig Magne Sollid

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

Stephen N. McAdam

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

Øyvind Molberg

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

Hanne Quarsten

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

Eva Helene Arentz-Hansen

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo
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