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Immunopathogenesis of celiac disease

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Abstract

Celiac disease is a chronic inflammatory disease caused by dietary gluten that affects 1% of Europeans and North Americans. Gluten is unusual because it is consumed in relatively large amounts, is partially resistant to luminal digestion in the human small intestine, and when absorbed, is susceptible to post-translational modification (deamidation) by mucosal transglutaminase. Deamidation of certain gluten peptides enhances their binding to HLA-DQ2 or HLA-DQ8 and creates neodeterminants capable of stimulating CD4+ T cells. Only 5% of individuals with HLA-DQ2 and 0.5% of those with HLA-DQ8 have celiac disease, so immunologic tolerance to gluten is the norm. The critical steps in the immunopathogenesis of celiac disease are broadly understood, but little is known regarding mechanisms of tolerance to gluten. The effectiveness of therapies being developed for celiac disease will test the accuracy of our current understanding of disease pathogenesis.

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Authors and Affiliations

  1. Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3050, Australia

    Robert Anderson

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  1. Jason Tye-Din
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  2. Robert Anderson
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Correspondence to Robert Anderson.

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Tye-Din, J., Anderson, R. Immunopathogenesis of celiac disease. Curr Gastroenterol Rep 10, 458–465 (2008). https://doi.org/10.1007/s11894-008-0085-9

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