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Stepniak, D.T. (2006)

Celiac disease : from basic insight to therapy development

Doctoral Thesis
Celiac disease (CD) is a common disorder of the small intestine caused by intolerance to gluten, proteins found in wheat and related cereals. In this study two major questions were addressed: i) which specific properties of gluten contribute to its disease-inducing characteristics ii) how can gluten toxicity be avoided. We found that CD-related molecule HLA-DQ2 has several features that explain why it can specifically interact with a large array of distinct gluten peptides. We also observed that some of the gluten peptides are being recognized by gluten-specific T cells in quite an unusual way, requiring the presence of a proline at position p-1. Another interesting observation was that the disease-inducing properties of rye and barley could be explained by the cross-reaction of gluten-specific T cells with the homologous peptides from these cereals. Although genetic studies indicated that the gene for prolyl endopeptidase could be involved in the pathogenesis of CD we showed that...Show moreCeliac disease (CD) is a common disorder of the small intestine caused by intolerance to gluten, proteins found in wheat and related cereals. In this study two major questions were addressed: i) which specific properties of gluten contribute to its disease-inducing characteristics ii) how can gluten toxicity be avoided. We found that CD-related molecule HLA-DQ2 has several features that explain why it can specifically interact with a large array of distinct gluten peptides. We also observed that some of the gluten peptides are being recognized by gluten-specific T cells in quite an unusual way, requiring the presence of a proline at position p-1. Another interesting observation was that the disease-inducing properties of rye and barley could be explained by the cross-reaction of gluten-specific T cells with the homologous peptides from these cereals. Although genetic studies indicated that the gene for prolyl endopeptidase could be involved in the pathogenesis of CD we showed that most likely this gene does not play a role in the disease development. Finally, we demonstrated that prolyl endoprotease from Aspergillus niger could be an effective measure to detoxify gluten in vitro.Show less
Gluten intolerance
HLA-DQ2
Prolyl endopeptidease
Prolyl endoprotease
T cell cross reactivity
All authors
Stepniak, D.T.
Supervisor
Supervisor: Koning F.
Qualification
Doctor (dr.)
Date
2006-12-14
ISBN (print)
9090212094