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Acta Endoscopica

, Volume 31, Issue 3, pp 255–264 | Cite as

Maladie cœllaque: facteurs génétiques et présentation des antigènes

  • S. Moodie
  • P. Ciclitira
Article
  • 45 Downloads

Résumé

La prévalence de la maladie cœliaque est plus élevée qu’on ne le pensait précédemment et l’affection reste sous diagnostiquée en particulier chez les patients présentant des symptômes peu évidents ou non spécifiques. L’importance du diagnostic, basé sur la biopsie duodénale perendoscopique et la réponse au régime sans gluten, est soulignée par la mise en évidence de l’accroissement des risques de malignité associée à la maladie auto-immune ainsi que de l’ostéoporose chez les patients soumis à un régime sans gluten. Dans cet article, nous discutons les progrès réalisés dans l’identification des gènes porteurs du risque de la maladie et la façon dont ceux-ci nous permettent d’identifier les mécanismes impliqués dans la présentation des gènes et dans l’immunologie de la maladie cœliaque. Une concordance de 70%vs 10% de l’incidence de la maladie chez les jumeaux monozygotes par comparaison aux apparentés démontre la nature héréditaire de la maladie. Le risque génétique est partagé entre le risque attribuable à la région HLA du chromosome 6 et celui attribué à un ou plusieurs gènes situés en dehors de ce site. Plus de 95% des patients atteints de maladie cœliaque sont porteurs de HLA de classe II avec un génotype DQ2 ou DQ8 encodant des molécules de classe II porteuses d’antigène spécifique capable de se lier aux peptides dérivés du gluten. Dans la maladie cœliaque, de petites cellules possèdent un antigène intestinal capable de se lier aux peptides dérivés du gluten par DQ2 ou DQ8 afin de les présenter aux cellules T sensibles au gluten, ce qui entraîne une inflammation intestinale. La liaison des peptides dérivés du gluten à DQ2 ou à DQ8 est nettement améliorée par la transglutaminase, une enzyme tissulaire qui augmente la charge négative des peptides de gluten par une déamination sélective des résidus de la glutamine. Ceci permet d’identifier les fragments peptidiques particuliers dérivés du gluten alimentaire qui contiennent le(s), épitope(s) capable(s) d’initier ou de maintenir la réponse immunitaire. La transglutaminase tissulaire peut aussi être identifiée comme cible des anticorps anti-endomysium présents chez plus de 90% des malades cœliaques ce qui conduit à spéculer sur le rôle central joué par cette enzyme ou peut-être les anticorps eux-mêmes dans la pathogenèse de la maladie cœliaque.

Mots-clés

génétique maladie cœliaque présentation des antigènes 

Coeliac disease: genetic factors and antigen presentation

Summary

The prevalence of coeliac disease is higher than previously thought and it remains underdiagnosed especially in patients with non-specific or mild symptoms. The importance of diagnosis, based on duodenal biopsy at endoscopy and response to a gluten free diet, is underlined by evidence of increased risk of malignancy, associated autoimmune disease and osteoporosis in patients remaining on a gluten containing diet. In this review, we discuss progress towards identifying the genes that carry the disease risk and how this has helped in identifying the mechanisms involved in antigen presentation and the immunology of coeliac disease. A disease concordance of 70% versus 10% for monozygotic twins compared to siblings demonstrates the strongly heritable nature of the disease. The genetic risk is divided between the risk attributable to the HLA region on chromosome 6 and the risk attributable to one or more genes outside this region. Over 95% of coeliac patients carry the HLA class II genotype DQ2 or DQ8 encoding class II molecules with specific antigen binding properties capable of binding gluten derived peptides. In coeliac disease, small intestinal antigen presenting cells present gluten derived peptides in association with either DQ2 or DQ8 to gluten sensitive T cells leading to small intestinal inflammation. The binding of gluten derived peptides to DQ2 and DQ8 is greatly enhanced by the action of the enzyme tissue transglutaminase in increasing the negative charge on gluten peptides by selective deamidation of glutamine residues. This has aided progress towards, identifying the particular peptide fragments derived from dietary gluten that contain the epitope(s) capable of initiating or maintaining the immune response. Tissue transglutaminase has also been identified as the target for the anti-endomyseal antibodies present in over 90% of coeliac patients leading to speculation of a central role for this enzyme and perhaps the antibodies themselves in the pathogenesis of coeliac disease.

Key-words

antigen presentation coeliac disease genetics 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  1. 1.Department of Gastroenterology (GKT), The Rayne InstituteSt. Thomas HospitalLondonEngland

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