Summary
Celiac disease (cd) is caused by a permanent intolerance to gluten. Gluten is a heterogeneous mixture of proteins termed gliadins and glutenins. Over 90% of the patients are hla-dq2 positive and the remainder is usually hla-dq8 positive. It is now well established that inflammatory hla-dq2 and/or -dq8 restricted, gluten-specific T cells are present at the site of the lesions in the gut and these are believed to cause disease. Several gluten peptides that are recognized by gut derived T cells from cd patients have now been identified. Moreover, it has been found that such peptides can be modified by the enzyme tissue transglutaminase (ttg) that is either required for or enhances T cell recognition. A number of key observations that have been made in recent years is briefly described and it is discussed how this has reshaped our thinking about cd development.
Samenvatting
Coeliakie is een ziekte van de dunne darm die het gevolg is van een intolerantie voor gluten. Gluten is een heterogeen mengsel van eiwitten afkomstig uit granen, gliadinen en gluteninen genaamd. Van deze moleculen bestaan vele varianten die in allerlei combinaties in tarwesoorten te vinden zijn. In elke tarwesoort komen daarom tussen de 50 en 100 verschillende glutenmoleculen voor. Meer dan 90% van de coeliakiepatiënten is hla-dq2-positief en de rest is meestal hla-dq8-positief. In de darm van coeliakiepatiënten zijn T-cellen aanwezig die reageren op van gluten afkomstige fragmenten (peptiden) die aan hla-dq2 of -dq8 gebonden zijn. De stimulatie van deze T-cellen leidt tot de secretie van inflammatoire cytokinen en deze T-celreacties worden dan ook verondersteld de ziekte te veroorzaken. Er is nu een hele serie van gliadine en glutenine afkomstige peptiden gekarakteriseerd die T-cellen uit de dunne darm van coeliakiepatiënten kunnen stimuleren. Er is bovendien gevonden dat zulke peptiden gemodificeerd kunnen worden door het enzym weefseltransglutaminase (ttg) en dat dit de T-celreactie op deze glutenpeptiden versterkt. In dit artikel worden de recente doorbraken in het onderzoek naar het ontstaan van coeliakie beschreven en wordt bediscussieerd hoe dit op termijn tot alternatieven voor de patiënt zal leiden.
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Dr. Frits Koning, afdeling Immunohematologie en Bloedtransfusie, Leids Universitair Medisch Centrum.
Correspondentieadres: Dr. F. Koning, afdeling Immunohematologie en Bloedtransfusie, Leids Universitair Medisch Centrum, Postbus 9600, 2300 RC Leiden,
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Koning, F. De immunologie van coeliakie. KIND 72, 7–12 (2004). https://doi.org/10.1007/BF03061528
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DOI: https://doi.org/10.1007/BF03061528