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Future therapeutic options for celiac disease


Celiac disease is a disorder of the small intestine caused by an inappropriate immune response to wheat gluten and similar proteins of barley and rye. At present, the only available treatment is a strict gluten-exclusion diet; hence the need for alternative treatments. Recent advances have improved our understanding of the molecular basis for this disorder and there are several attractive targets for new treatments. Oral enzyme supplementation is designed to accelerate gastrointestinal degradation of proline-rich gluten, especially its proteolytically stable antigenic peptides. Complementary strategies aiming to interfere with activation of gluten-reactive T cells include the inhibition of intestinal tissue transglutaminase activity to prevent selective deamidation of gluten peptides, and blocking the binding of gluten peptides to the HLA-DQ2 or HLA-DQ8 molecules. Other possible treatments include cytokine therapy, and selective adhesion molecule inhibitors that interfere with inflammatory reactions, some of which are already showing promise in the clinic for other gastrointestinal diseases.

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Figure 1: The small-intestinal lesion in patients with celiac disease.


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Work by the authors was supported in part by grants from the Research Council of Norway, the NIH and the European Commission.

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Correspondence to Ludvig M Sollid.

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Ludvig M Sollid and Chaitan Khosla are involved in non-profit organizations that develop new treatments for celiac disease. Chaitan Khosla is the President of the Celiac Sprue Research Foundation, and Ludvig M Sollid is a member of the scientific advisory boards of the Celiac Sprue Research Foundation and the National Foundation for Celiac Awareness.



Wheat gluten remains after washing dough and consists of a complex mixture of many gliadin and glutenin polypeptides; gluten-like proteins are also found in rye and barley


HLA-DQ2 (DQA1*05/DQB1*02) and HLA-DQ8 (DQA1*03/DQB1*0302) are HLA (human leukocyte antigen) molecules associated with celiac disease


The modification of glutamine residues in peptides and proteins to glutamate, or asparagine residues to aspartate


An enzyme responsible for modifying proteins/peptides by transamidation/deamidation of specific glutamine residues; patients with celiac disease have IgA and IgG antibodies against TG2


MHC class-I like molecule expressed on gut epithelium; MIC is a ligand for NKG2D


Activating receptor of natural killer cells and CD8+ T cells; NKG2D is expressed on most intraepithelial lymphocytes


A site on an antigen that is recognized by an antigen receptor (i.e. antibody or T-cell receptor)


A type of CD4+ T-cell immune response characterized primarily by the production of interferon-γ


A lytic and antagonistic IL-15 mutant/Fcgamma2a fusion protein that targets interleukin-15 receptor


A cell-surface protein that is involved in cell–cell and cell–matrix interactions


A mouse strain (nonobese diabetic) that spontaneously develops autoimmune diabetes


A protein for which the gene is not yet cloned that regulates the permeability of the intestine

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Sollid, L., Khosla, C. Future therapeutic options for celiac disease. Nat Rev Gastroenterol Hepatol 2, 140–147 (2005).

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