Studies of the role of glycans in IBD are focused on three areas: glycosylation patterns of intestinal mucins, serum glycan levels of glycoproteins involved in inflammation, and colonic expression of glycan receptors
The carbohydrate content of mucus glycoproteins has been found to be reduced in patients with active ulcerative colitis compared with healthy controls
This finding provides an explanation for the role of glycans in IBD development, by suggesting that a defective inner mucus layer leads to increased bacterial contact with the epithelium that triggers inflammation
Decreased galactosylation of circulating IgG has been found in patients with ulcerative colitis compared with healthy controls, a finding that is relevant for effector functions of IgG
P-selectin and L-selectin are upregulated in IBD, which might be relevant for the development of new therapies, as pharmacological blockade of selectins has been demonstrated to ameliorate disease pathology in various diseases
The association between serum levels of mannose binding lectin and IBD has been analysed in many studies, but no link has been reported
A number of genetic and immunological studies give impetus for investigating the role of glycosylation in IBD. Experimental mouse models have helped to delineate the role of glycosylation in intestinal mucins and to explore the putative pathogenic role of glycosylation in colitis. These experiments have been extended to human studies investigating the glycosylation patterns of intestinal mucins as well as levels of glycans of serum glycoproteins and expression of glycan receptors. These early human studies have generated interesting hypotheses regarding the pathogenic role of glycans in IBD, but have generally been restricted to fairly small underpowered studies. Decreased glycosylation has been observed in the intestinal mucus of patients with IBD, suggesting that a defective inner mucus layer might lead to increased bacterial contact with the epithelium, potentially triggering inflammation. In sera, decreased galactosylation of IgG has been suggested as a diagnostic marker for IBD. Advances in glycoprofiling technology make it technically feasible and affordable to perform high-throughput glycan pattern analyses and to build on previous work investigating a much wider range of glycan parameters in large numbers of patients.
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E.T. and H.C. are joint first authors, and J.S. and G.L. are joint last authors. The authors acknowledge the work of the IBD-BIOM group.
N.P.B. works for Genos Ltd, a private research organization that specializes in high-throughput glycomic analysis. D.F. is the CEO of Ludger Ltd, a commercial company that specializes in the development and validation of glycoprofiling technology for biologic therapeutics and biological tissues. There are no patents, products in development or marketed products to declare. I.K.P. is the Research Director of IP Research Consulting SAS, a privately-owned, research intensive SME under the commercial name of Photeomix Protein Discovery that specializes in the discovery and validation of biomarkers based on post-translational protein modification activities. There are no patents, products in development or marketed products to declare. G. L. is founder and owner of Genos Ltd. These competing interests do not alter the authors' adherence to all the Nature Publishing Group rules or other rules that might be perceived to influence the interpretation of the article. All other authors declare no competing interests.
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Theodoratou, E., Campbell, H., Ventham, N. et al. The role of glycosylation in IBD. Nat Rev Gastroenterol Hepatol 11, 588–600 (2014). https://doi.org/10.1038/nrgastro.2014.78
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