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The role of glycosylation in IBD

Nature Reviews Gastroenterology & Hepatology volume 11, pages 588–600 (2014)Cite this article

Subjects

Key Points

  • 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

Abstract

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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Figure 1: The major classes of N-glycans and O-glycans frequently found on human glycoproteins and selected examples.
Figure 2: Structure and polymerisation of mucin 2 (MUC2) monomer.
Figure 3: The squamous epithelium of the mouth and oesophagus is washed by mucus from the salivary glands.
Figure 4: Human IgG1 fragment crystallisable region (Fc).
Figure 5: Glycan receptors.

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References

  1. Hart, G. W. & Copeland, R. J. Glycomics hits the big time. Cell 143, 672–676 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Zielinska, D. F., Gnad, F., Wisniewski, J. R. & Mann, M. Precision mapping of an in vivo N-glycoproteome reveals rigid topological and sequence constraints. Cell 141, 897–907 (2010).

    CAS  PubMed  Google Scholar 

  3. Moran, A. P., Gupta, A. & Joshi, L. Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 60, 1412–1425 (2011).

    CAS  PubMed  Google Scholar 

  4. Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2095–2128 (2012).

    PubMed  Google Scholar 

  5. Murray, C. J. et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2197–2223 (2012).

    PubMed  Google Scholar 

  6. Garrett, W. S., Gordon, J. I. & Glimcher, L. H. Homeostasis and inflammation in the intestine. Cell 140, 859–870 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. van der Post, S. et al. Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB). J. Biol. Chem. 288, 14636–14646 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Xavier, R. J. & Podolsky, D. K. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007).

    CAS  PubMed  Google Scholar 

  10. Franke, A. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42, 1118–1125 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Franke, A. et al. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). Nat. Genet. 42, 292–294 (2010).

    CAS  PubMed  Google Scholar 

  12. Anderson, C. A. et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43, 246–252 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lauc, G. et al. Genomics meets glycomics-the first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation. PLoS Genet. 6, e1001256 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Barrett, J. C. et al. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat. Genet. 41, 1330–1334 (2009).

    CAS  PubMed  Google Scholar 

  16. McGovern, D. P. et al. Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Hum. Mol. Genet. 19, 3468–3476 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Becker, D. J. & Lowe, J. B. Fucose: biosynthesis and biological function in mammals. Glycobiology 13, 41R–53R (2003).

    CAS  PubMed  Google Scholar 

  18. Smith, P. L. et al. Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J. Cell Biol. 158, 801–815 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Lauc, G. et al. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. PLoS Genet. 9, e1003225 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kaneko, Y., Nimmerjahn, F. & Ravetch, J. V. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313, 670–673 (2006).

    CAS  PubMed  Google Scholar 

  21. Thanabalasingham, G. et al. Mutations in HNF1A result in marked alterations of plasma glycan profile. Diabetes 62, 1329–1337 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Harvey, D. J., Merry, A. H., Royle, L., Campbell, M. P. & Rudd, P. M. Symbol nomenclature for representing glycan structures: Extension to cover different carbohydrate types. Proteomics 11, 4291–4295 (2011).

    CAS  PubMed  Google Scholar 

  23. Moremen, K. W., Tiemeyer, M. & Nairn, A. V. Vertebrate protein glycosylation: diversity, synthesis and function. Nat. Rev. Mol. Cell Biol. 13, 448–462 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Gornik, O., Pavic, T. & Lauc, G. Alternative glycosylation modulates function of IgG and other proteins—implications on evolution and disease. Biochim. Biophys. Acta 1820, 1318–1326 (2012).

    CAS  PubMed  Google Scholar 

  25. Zachara, N. E. & Hart, G. W. Cell signaling, the essential role of O-GlcNAc! Biochim. Biophys. Acta 1761, 599–617 (2006).

    CAS  PubMed  Google Scholar 

  26. Marek, K. W., Vijay, I. K. & Marth, J. D. A recessive deletion in the GlcNAc-1-phosphotransferase gene results in peri-implantation embryonic lethality. Glycobiology 9, 1263–1271 (1999).

    CAS  PubMed  Google Scholar 

  27. Freeze, H. H. Genetic defects in the human glycome. Nat. Rev. Genet. 7, 537–551 (2006).

    CAS  PubMed  Google Scholar 

  28. Pucic, M. et al. High throughput isolation and glycosylation analysis of IgG-variability and heritability of the IgG glycome in three isolated human populations. Mol. Cell Proteomics 10, M111.010090 (2011).

    PubMed  PubMed Central  Google Scholar 

  29. Knezevic, A. et al. Variability, heritability and environmental determinants of human plasma N-glycome. J. Proteome Res. 8, 694–701 (2009).

    CAS  PubMed  Google Scholar 

  30. Pucic, M. et al. Common aberrations from the normal human plasma N-glycan profile. Glycobiology 20, 970–975 (2010).

    CAS  PubMed  Google Scholar 

  31. National Research Council. Transforming Glycoscience: a Roadmap for the Future (the National Academies Press, 2012).

  32. Johansson, M. E., Sjovall, H. & Hansson, G. C. The gastrointestinal mucus system in health and disease. Nat. Rev. Gastroenterol. Hepatol. 10, 352–361 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Bennett, E. P. et al. Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family. Glycobiology 22, 736–756 (2012).

    CAS  PubMed  Google Scholar 

  34. Holmen Larsson, J. M., Thomsson, K. A., Rodriguez-Pineiro, A. M., Karlsson, H. & Hansson, G. C. Studies of mucus in mouse stomach, small intestine, and colon. III. Gastrointestinal Muc5ac and Muc2 mucin O-glycan patterns reveal a regiospecific distribution. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G357–G363 (2013).

    PubMed  PubMed Central  Google Scholar 

  35. Ermund, A., Schutte, A., Johansson, M. E., Gustafsson, J. K. & Hansson, G. C. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G341–G347 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Van der Sluis, M. et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117–129 (2006).

    CAS  PubMed  Google Scholar 

  37. Johansson, M. E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl Acad. Sci. USA 105, 15064–15069 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Kaser, A. et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134, 743–756 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Heazlewood, C. K. et al. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 5, e54 (2008).

    PubMed  PubMed Central  Google Scholar 

  40. Fu, J. et al. Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice. J. Clin. Invest. 121, 1657–1666 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Johansson, M. E. et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 63, 281–291 (2014).

    CAS  PubMed  Google Scholar 

  42. Johansson, M. E. et al. Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model. PLoS ONE 5, e12238 (2010).

    PubMed  PubMed Central  Google Scholar 

  43. Campbell, B. J., Finnie, I. A., Hounsell, E. F. & Rhodes, J. M. Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. J. Clin. Invest. 95, 571–576 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Clamp, J. R., Fraser, G. & Read, A. E. Study of the carbohydrate content of mucus glycoproteins from normal and diseased colons. Clin. Sci. 61, 229–234 (1981).

    CAS  Google Scholar 

  45. Larsson, J. M. H. et al. Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation. Inflamm. Bowel Dis. 17, 2299–2307 (2011).

    PubMed  Google Scholar 

  46. Teague, R. H., Fraser, D. & Clamp, J. R. Changes in monosaccharide content of mucous glycoproteins in ulcerative colitis. BMJ 2, 645–646 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Cassel, S. L., Sutterwala, F. S. & Flavell, R. A. The tiny conductor: immune regulation via commensal organisms. Cell Host Microbe 3, 340–341 (2008).

    CAS  PubMed  Google Scholar 

  48. Rhodes, J. M., Black, R. R. & Savage, A. Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn's disease. Dig. Dis. Sci. 33, 1359–1363 (1988).

    CAS  PubMed  Google Scholar 

  49. Cooper, H. S., Farano, P. & Coapman, R. A. Peanut lectin binding sites in colons of patients with ulcerative colitis. Arch. Pathol. Lab. Med. 111, 270–275 (1987).

    CAS  PubMed  Google Scholar 

  50. Boland, C. R. Mucin glycoproteins in chronic ulcerative colitis. Peanut lectin binding in human and nonhuman primate colons. Dig. Dis. Sci. 30, 147S–153S (1985).

    CAS  PubMed  Google Scholar 

  51. Boland, C. R., Lance, P., Levin, B., Riddell, R. H. & Kim, Y. S. Abnormal goblet cell glycoconjugates in rectal biopsies associated with an increased risk of neoplasia in patients with ulcerative colitis: early results of a prospective study. Gut 25, 1364–1371 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Carneiro, F. et al. T (Thomsen-Friedenreich) antigen and other simple mucin-type carbohydrate antigens in precursor lesions of gastric carcinoma. Histopathology 24, 105–113 (1994).

    CAS  PubMed  Google Scholar 

  53. Dabelsteen, E., Clausen, H., Holmstrup, P. & Reibel, J. Premalignant and malignant oral lesions are associated with changes in the glycosylation pattern of carbohydrates related to ABH blood group antigens. APMIS 96, 813–819 (1988).

    CAS  PubMed  Google Scholar 

  54. Springer, G. F., Desai, P. R., Ghazizadeh, M. & Tegtmeyer, H. T/Tn pancarcinoma autoantigens: fundamental, diagnostic, and prognostic aspects. Cancer Detect. Prev. 19, 173–182 (1995).

    CAS  PubMed  Google Scholar 

  55. Springer, G. F. Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J. Mol. Med. (Berl.) 75, 594–602 (1997).

    CAS  Google Scholar 

  56. Springer, G. F. T and Tn, general carcinoma autoantigens. Science 224, 1198–1206 (1984).

    CAS  PubMed  Google Scholar 

  57. Bodger, K. et al. Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients. Gut 55, 973–977 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Swidsinski, A. et al. Comparative study of the intestinal mucus barrier in normal and inflamed colon. Gut 56, 343–350 (2007).

    PubMed  Google Scholar 

  59. Johansson, M. E. et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 63, 281–291 (2014).

    CAS  PubMed  Google Scholar 

  60. Lidell, M. E., Moncada, D. M., Chadee, K. & Hansson, G. C. Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel. Proc. Natl Acad. Sci. USA 103, 9298–9303 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. An, G. et al. Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J. Exp. Med. 204, 1417–1429 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Camacho, F. I. et al. CD44v6 expression in inflammatory bowel disease is associated with activity detected by endoscopy and pathological features. Histopathology 35, 144–149 (1999).

    CAS  PubMed  Google Scholar 

  63. Rosenberg, W. M. et al. Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not colonic Crohn's disease. Lancet 345, 1205–1209 (1995).

    CAS  PubMed  Google Scholar 

  64. Campbell, B. J., Yu, L. G. & Rhodes, J. M. Altered glycosylation in inflammatory bowel disease: a possible role in cancer development. Glycoconj. J. 18, 851–858 (2001).

    CAS  PubMed  Google Scholar 

  65. Rottger, S. et al. Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus. J. Cell Sci. 111, 45–60 (1998).

    CAS  PubMed  Google Scholar 

  66. Campbell, B. J., Rowe, G. E., Leiper, K. & Rhodes, J. M. Increasing the intra-Golgi pH of cultured LS174T goblet-differentiated cells mimics the decreased mucin sulfation and increased Thomsen-Friedenreich antigen (Gal beta1–3GalNac alpha-) expression seen in colon cancer. Glycobiology 11, 385–393 (2001).

    CAS  PubMed  Google Scholar 

  67. Kaneko, Y. et al. Altered expression of CDX-2, PDX-1 and mucin core proteins in “Ulcer-associated cell lineage (UACL)” in Crohn's disease. J. Mol. Histol. 39, 161–168 (2008).

    CAS  PubMed  Google Scholar 

  68. Arnold, J. N., Saldova, R., Hamid, U. M. & Rudd, P. M. Evaluation of the serum N-linked glycome for the diagnosis of cancer and chronic inflammation. Proteomics 8, 3284–3293 (2008).

    CAS  PubMed  Google Scholar 

  69. Miyahara, K. et al. Serum glycan markers for evaluation of disease activity and prediction of clinical course in patients with ulcerative colitis. PLoS ONE 8, e74861 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Parekh, R. B. et al. Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 316, 452–457 (1985).

    CAS  PubMed  Google Scholar 

  71. Davidson, A. & Diamond, B. Autoimmune diseases. N. Engl. J. Med. 345, 340–350 (2001).

    CAS  PubMed  Google Scholar 

  72. Herszenyi, L. & Tulassay, Z. The role of autoantibodies in inflammatory bowel disease. Dig. Dis. 30, 201–207 (2012).

    PubMed  Google Scholar 

  73. Surolia, I. et al. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 466, 243–247 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Aschermann, S., Lux, A., Baerenwaldt, A., Biburger, M. & Nimmerjahn, F. The other side of immunoglobulin G: suppressor of inflammation. Clin. Exp. Immunol. 160, 161–167 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Fujii, S., Nishiura, T., Nishikawa, A., Miura, R. & Taniguchi, N. Structural heterogeneity of sugar chains in immunoglobulin, G. Conformation of immunoglobulin G molecule and substrate specificities of glycosyltransferases. J. Biol. Chem. 265, 6009–6018 (1990).

    CAS  PubMed  Google Scholar 

  76. Karsten, C. M. et al. Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcgammaRIIB and dectin-1. Nat. Med. 18, 1401–1406 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Dube, R. et al. Agalactosyl IgG in inflammatory bowel disease: correlation with C-reactive protein. Gut 31, 431–434 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Shinzaki, S. et al. IgG oligosaccharide alterations are a novel diagnostic marker for disease activity and the clinical course of inflammatory bowel disease. Am. J. Gastroenterol. 103, 1173–1181 (2008).

    PubMed  Google Scholar 

  79. Singh, K., Chang, C. & Gershwin, M. E. IgA deficiency and autoimmunity. Autoimmun. Rev. 13, 163–177 (2014).

    CAS  PubMed  Google Scholar 

  80. Mattu, T. S. et al. The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fcalpha receptor interactions. J. Biol. Chem. 273, 2260–2272 (1998).

    CAS  PubMed  Google Scholar 

  81. Inoue, T. et al. Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease. Inflamm. Bowel Dis. 18, 1723–1734 (2012).

    PubMed  Google Scholar 

  82. Inoue, T. et al. O-linked oligosaccharide alterations of IgA1 are a novel biological marker of patients with inflammatory bowel disease. Dig. Dis. Sci. 56, 2772 (2011).

    Google Scholar 

  83. Levy, A. P. et al. Haptoglobin: basic and clinical aspects. Antioxid. Redox Signal. 12, 293–304 (2010).

    CAS  PubMed  Google Scholar 

  84. Treuheit, M. J., Costello, C. E. & Halsall, H. B. Analysis of the five glycosylation sites of human alpha 1-acid glycoprotein. Biochem. J. 283, 105–112 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Goodarzi, M. T. & Turner, G. A. Reproducible and sensitive determination of charged oligosaccharides from haptoglobin by PNGase F digestion and HPAEC/PAD analysis: glycan composition varies with disease. Glycoconj. J. 15, 469–475 (1998).

    CAS  PubMed  Google Scholar 

  86. Park, S.-Y. et al. Dimeric Lea (Lea-on-Lea) status of β-haptoglobin in sera of colon cancer, chronic inflammatory disease and normal subjects. Int. J. Oncol. 36, 1291–1297 (2010).

    CAS  PubMed  Google Scholar 

  87. Park, S. Y. et al. N-glycosylation status of β-haptoglobin in sera of patients with colon cancer, chronic inflammatory diseases and normal subjects. Int. J. Cancer 126, 142–155 (2010).

    CAS  PubMed  Google Scholar 

  88. Park, S. Y. et al. α1–3/4 fucosylation at Asn 241 of β-haptoglobin is a novel marker for colon cancer: A combinatorial approach for development of glycan biomarkers. Int. J. Cancer 130, 2366–2376 (2012).

    CAS  PubMed  Google Scholar 

  89. Ryden, I., Skude, G., Lundblad, A. & Pahlsson, P. Glycosylation of alpha1-acid glycoprotein in inflammatory disease: analysis by high-pH anion-exchange chromatography and concanavalin A crossed affinity immunoelectrophoresis. Glycoconj. J. 14, 481–488 (1997).

    CAS  PubMed  Google Scholar 

  90. Ghazarian, H., Idoni, B. & Oppenheimer, S. B. A glycobiology review: carbohydrates, lectins and implications in cancer therapeutics. Acta Histochem. 113, 236–247 (2011).

    CAS  PubMed  Google Scholar 

  91. Smith, D. F., Song, X. & Cummings, R. D. Use of glycan microarrays to explore specificity of glycan-binding proteins. Methods Enzymol. 480, 417–444 (2010).

    CAS  PubMed  Google Scholar 

  92. Sharon, N. & Lis, H. History of lectins: from hemagglutinins to biological recognition molecules. Glycobiology 14, 53R–62R (2004).

    CAS  PubMed  Google Scholar 

  93. Wagner, D. D. & Frenette, P. S. The vessel wall and its interactions. Blood 111, 5271–5281 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Polinska, B., Matowicka-Karna, J. & Kemona, H. Assessment of the influence of the inflammatory process on the activation of blood platelets and morphological parameters in patients with ulcerative colitis (colitis ulcerosa). Folia Histochem. Cytobiol. 49, 119–124 (2011).

    PubMed  Google Scholar 

  95. Pamuk, G. E. et al. Increased circulating platelet-neutrophil, platelet-monocyte complexes, and platelet activation in patients with ulcerative colitis: a comparative study. Am. J. Hematol. 81, 753–759 (2006).

    CAS  PubMed  Google Scholar 

  96. Kayo, S. et al. Close association between activated platelets and neutrophils in the active phase of ulcerative colitis in humans. Inflamm. Bowel Dis. 12, 727–735 (2006).

    PubMed  Google Scholar 

  97. Andoh, A. et al. Elevated circulating platelet-derived microparticles in patients with active inflammatory bowel disease. Am. J. Gastroenterol. 100, 2042–2048 (2005).

    CAS  PubMed  Google Scholar 

  98. Irving, P. M. et al. Formation of platelet-leukocyte aggregates in inflammatory bowel disease. Inflamm. Bowel Dis. 10, 361–372 (2004).

    PubMed  Google Scholar 

  99. Magro, F. et al. Soluble selectins, sICAM, sVCAM, and angiogenic proteins in different activity groups of patients with inflammatory bowel disease. Dig. Dis. Sci. 49, 1265–1274 (2004).

    CAS  PubMed  Google Scholar 

  100. Suzuki, K. et al. Activated platelets in ulcerative colitis enhance the production of reactive oxygen species by polymorphonuclear leukocytes. Scand. J. Gastroenterol. 36, 1301–1306 (2001).

    CAS  PubMed  Google Scholar 

  101. Goke, M., Hoffmann, J. C., Evers, J., Kruger, H. & Manns, M. P. Elevated serum concentrations of soluble selectin and immunoglobulin type adhesion molecules in patients with inflammatory bowel disease. J. Gastroenterol. 32, 480–486 (1997).

    CAS  PubMed  Google Scholar 

  102. Schurmann, G. M. et al. Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease. Gut 36, 411–418 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Collins, C. E., Cahill, M. R., Newland, A. C. & Rampton, D. S. Platelets circulate in an activated state in inflammatory bowel disease. Gastroenterology 106, 840–845 (1994).

    CAS  PubMed  Google Scholar 

  104. Nakamura, S. et al. In situ expression of the cell adhesion molecules in inflammatory bowel disease. Evidence of immunologic activation of vascular endothelial cells. Lab. Invest. 69, 77–85 (1993).

    CAS  PubMed  Google Scholar 

  105. Huang, Q., Wang, E., Lin, M., Yan, X. & Zhang, Y. Analysis of P-selectin and platelet parameters in patients with ulcerative colitis. [Chinese]. Chin. J. Gastroenterol. 17, 430–432 (2012).

    Google Scholar 

  106. Gao, Y. H. et al. Relationship and significance between anti-beta2-glycoprotein I antibodies and platelet activation state in patients with ulcerative colitis. World J. Gastroenterol. 14, 771–775 (2008).

    PubMed  PubMed Central  Google Scholar 

  107. Zarbock, A., Polanowska-Grabowska, R. K. & Ley, K. Platelet–neutrophil–interactions: linking hemostasis and inflammation. Blood Rev. 21, 99–111 (2007).

    CAS  PubMed  Google Scholar 

  108. Bedard, P. W. & Kaila, N. Selectin inhibitors: a patent review. Expert Opin. Ther. Pat. 20, 781–793 (2010).

    CAS  PubMed  Google Scholar 

  109. Goggins, M. G. et al. Soluble adhesion molecules in inflammatory bowel disease. Irish J. Med. Sci. 170, 107–111 (2001).

    CAS  PubMed  Google Scholar 

  110. Bhatti, M., Chapman, P., Peters, M., Haskard, D. & Hodgson, H. J. Visualising E-selectin in the detection and evaluation of inflammatory bowel disease. Gut 43, 40–47 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Cellier, C. et al. In-situ endothelial cell adhesion molecule expression in ulcerative colitis. E-selectin in-situ expression correlates with clinical, endoscopic and histological activity and outcome. Eur. J. Gastroenterol. Hepatol. 9, 1197–1203 (1997).

    CAS  PubMed  Google Scholar 

  112. Nielsen, O. H., Brynskov, J. & Vainer, B. Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis. Dig. Dis. Sci. 41, 1780–1785 (1996).

    CAS  PubMed  Google Scholar 

  113. Patel, R. T., Pall, A. A., Adu, D. & Keighley, M. R. Circulating soluble adhesion molecules in inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol. 7, 1037–1041 (1995).

    CAS  PubMed  Google Scholar 

  114. Oshitani, N. et al. Adhesion molecule expression on vascular endothelium and nitroblue tetrazolium reducing activity in human colonic mucosa. Scand. J. Gastroenterol. 30, 915–920 (1995).

    CAS  PubMed  Google Scholar 

  115. Pooley, N., Ghosh, L. & Sharon, P. Up-regulation of E-selectin and intercellular adhesion molecule-1 differs between Crohn's disease and ulcerative colitis. Dig. Dis. Sci. 40, 219–225 (1995).

    CAS  PubMed  Google Scholar 

  116. Gulubova, M. V., Manolova, I. M., Vlaykova, T. I., Prodanova, M. & Jovchev, J. P. Adhesion molecules in chronic ulcerative colitis. Int. J. Colorect. Dis. 22, 581–589 (2007).

    Google Scholar 

  117. Arihiro, S. et al. Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Pathol. Int. 52, 367–374 (2002).

    CAS  PubMed  Google Scholar 

  118. Lazaris, A. C., Dicoglou, C., Tseleni-Balafouta, S., Paraskevakou, H. & Davaris, P. S. In situ expression of E-selectin and intercellular adhesion molecule-1 in chronic inflammatory diseases of the gastrointestinal tract. APMIS 107, 819–827 (1999).

    CAS  PubMed  Google Scholar 

  119. Vainer, B., Nielsen, O. H. & Horn, T. Expression of E-selectin, sialyl Lewis X, and macrophage inflammatory protein-1alpha by colonic epithelial cells in ulcerative colitis. Dig. Dis. Sci. 43, 596–608 (1998).

    CAS  PubMed  Google Scholar 

  120. Jones, S. C. et al. Adhesion molecules in inflammatory bowel disease. Gut 36, 724–730 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Vainer, B. & Nielsen, O. H. Serum concentration and chemotactic activity of E-selectin (CD62E) in inflammatory bowel disease. Mediators Inflamm. 3, 215–218 (1994).

    Google Scholar 

  122. Rafiee, P. et al. Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC). Am. J. Physiol. Gastrointest. Liver Physiol. 298, G167–G176 (2010).

    CAS  PubMed  Google Scholar 

  123. Ley, K. Sulfated sugars for rolling lymphocytes. J. Exp. Med. 198, 1285–1288 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Seidelin, J. B., Vainer, B., Horn, T. & Nielsen, O. H. Circulating L-selectin levels and endothelial CD34 expression in inflammatory bowel disease. Am. J. Gastroenterol. 93, 1854–1859 (1998).

    CAS  PubMed  Google Scholar 

  125. Irving, P. M. et al. Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis. Eur. J. Gastroenterol. Hepatol. 20, 283–289 (2008).

    CAS  PubMed  Google Scholar 

  126. Suzawa, K. et al. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am. J. Gastroenterol. 102, 1499–1509 (2007).

    CAS  PubMed  Google Scholar 

  127. Kobayashi, M. et al. GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm. Bowel Dis. 15, 697–706 (2009).

    PubMed  Google Scholar 

  128. Feagan, B. G. et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 369, 699–710 (2013).

    CAS  PubMed  Google Scholar 

  129. Sandborn, W. J. et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N. Engl. J. Med. 369, 711–721 (2013).

    CAS  PubMed  Google Scholar 

  130. Targan, S. R. et al. Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial. Gastroenterology 132, 1672–1683 (2007).

    CAS  PubMed  Google Scholar 

  131. Rivera-Nieves, J. et al. L-selectin, alpha 4 beta 1, and alpha 4 beta 7 integrins participate in CD4+ T cell recruitment to chronically inflamed small intestine. J. Immunol. 174, 2343–2352 (2005).

    CAS  PubMed  Google Scholar 

  132. Schon, M. P., Drewniok, C. & Boehncke, W. H. Targeting selectin functions in the therapy of psoriasis. Curr. Drug Targets Inflamm. Allergy 3, 163–168 (2004).

    PubMed  Google Scholar 

  133. Chataway, J. & Miller, D. H. Natalizumab therapy for multiple sclerosis. Neurotherapeutics 10, 19–28 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Danese, S. New therapies for inflammatory bowel disease: from the bench to the bedside. Gut 61, 918–932 (2012).

    CAS  PubMed  Google Scholar 

  135. Papp, M. et al. Mannose-binding lectin level and deficiency is not associated with inflammatory bowel diseases, disease phenotype, serology profile, and NOD2/CARD15 genotype in a large Hungarian cohort. Hum. Immunol. 71, 407–413 (2010).

    CAS  PubMed  Google Scholar 

  136. Zimmermann-Nielsen, E., Baatrup, G., Thorlacius-Ussing, O., Agnholt, J. & Svehag, S. E. Complement activation mediated by mannan-binding lectin in plasma from healthy individuals and from patients with SLE, Crohn's disease and colorectal cancer. Suppressed activation by SLE plasma. Scand. J. Immunol. 55, 105–110 (2002).

    CAS  PubMed  Google Scholar 

  137. Nakajima, S. et al. Functional analysis of agalactosyl IgG in inflammatory bowel disease patients. Inflamm. Bowel Dis. 17, 927–936 (2011).

    PubMed  Google Scholar 

  138. Hoffmann, C. et al. Is there a role for mannan-binding lectin in the diagnosis of inflammatory bowel disease? Immunogenetics 62, 231–235 (2010).

    CAS  PubMed  Google Scholar 

  139. Schoepfer, A. M. et al. Low Mannan-binding lectin serum levels are associated with complicated Crohn's disease and reactivity to oligomannan (ASCA). Am. J. Gastroenterol. 104, 2508–2516 (2009).

    CAS  PubMed  Google Scholar 

  140. Seibold, F. et al. Association of deficiency for mannan-binding lectin with anti-mannan antibodies in Crohn's disease: a family study. Inflamm. Bowel Dis. 13, 1077–1082 (2007).

    PubMed  Google Scholar 

  141. Nielsen, R. G. et al. Genetic polymorphisms of mannan binding lectin (MBL), serum levels of MBL, the MBL associated serine protease and H-ficolin in patients with Crohn's disease. Gut 56, 311–312 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Seibold, F. et al. Genetic variants of the mannan-binding lectin are associated with immune reactivity to mannans in Crohn's disease. Gastroenterology 127, 1076–1084 (2004).

    CAS  PubMed  Google Scholar 

  143. Lippert, E. et al. Regulation of galectin-3 function in mucosal fibroblasts: potential role in mucosal inflammation. Clin. Exp. Immunol. 152, 285–297 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Shan, M. et al. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342, 447–453 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Zhao, X. et al. Evaluation of p38 MAPK pathway as a molecular signature in ulcerative colitis. J. Proteome Res. 10, 2216–2225 (2011).

    CAS  PubMed  Google Scholar 

  146. Muller, S. et al. Galectin-3 modulates T cell activity and is reduced in the inflamed intestinal epithelium in IBD. Inflamm. Bowel Dis. 12, 588–597 (2006).

    PubMed  Google Scholar 

  147. Jensen-Jarolim, E. et al. The constitutive expression of galectin-3 is downregulated in the intestinal epithelia of Crohn's disease patients, and tumour necrosis factor alpha decreases the level of galectin-3-specific mRNA in HCT-8 cells. Eur. J. Gastroenterol. Hepatol. 14, 145–152 (2002).

    CAS  PubMed  Google Scholar 

  148. Frol'ová, L. et al. Detection of galectin-3 in patients with inflammatory bowel diseases: New serum marker of active forms of IBD? Inflamm. Res. 58, 503–512 (2009).

    PubMed  Google Scholar 

  149. Morimoto, K. et al. Dysregulated upregulation of T-cell immunoglobulin and mucin domain-3 on mucosal T helper 1 cells in patients with Crohn's disease. Scand. J. Gastroenterol. 46, 701–709 (2011).

    CAS  PubMed  Google Scholar 

  150. Shi, F. et al. Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T cell function in ulcerative colitis. Clin. Immunol. 145, 230–240 (2012).

    CAS  PubMed  Google Scholar 

  151. Masuda, K. et al. Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity. Mol. Immunol. 44, 3122–3131 (2007).

    CAS  PubMed  Google Scholar 

  152. Iida, S. et al. Nonfucosylated therapeutic IgG1 antibody can evade the inhibitory effect of serum immunoglobulin G on antibody-dependent cellular cytotoxicity through its high binding to FcγRIIIa. Clin. Cancer Res. 12, 2879–2887 (2006).

    CAS  PubMed  Google Scholar 

  153. Scanlan, C. N., Burton, D. R. & Dwek, R. A. Making autoantibodies safe. Proc. Natl Acad. Sci. USA 105, 4081–4082 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Preithner, S. et al. High concentrations of therapeutic IgG1 antibodies are needed to compensate for inhibition of antibody-dependent cellular cytotoxicity by excess endogenous immunoglobulin G. Mol. Immunol. 43, 1183–1193 (2006).

    CAS  PubMed  Google Scholar 

  155. Shinkawa, T. et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J. Biol. Chem. 278, 3466–3473 (2003).

    CAS  PubMed  Google Scholar 

  156. Kolarich, D. et al. The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting mass-spectrometry-based glycoanalytic data. Mol. Cell. Proteomics 12, 991–995 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Landis, S. C. et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490, 187–191 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Gornik, O. & Lauc, G. Glycosylation of serum proteins in inflammatory diseases. Dis. Markers 25, 267–278 (2008).

    CAS  PubMed  Google Scholar 

  159. Gornik, O. & Lauc, G. Enzyme linked lectin assay (ELLA) for direct analysis of transferrin sialylation in serum samples. Clin. Biochem. 40, 718–723 (2007).

    CAS  PubMed  Google Scholar 

  160. Stockmann, H., Adamczyk, B., Hayes, J. & Rudd, P. M. Automated, high-throughput IgG-antibody glycoprofiling platform. Anal. Chem. 85, 8841–8849 (2013).

    CAS  PubMed  Google Scholar 

  161. Austrup, F. et al. P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues. Nature 385, 81–83 (1997).

    CAS  PubMed  Google Scholar 

  162. Lasky, L. A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science 258, 964–969 (1992).

    CAS  PubMed  Google Scholar 

  163. Lasky, L. A. Selectin-carbohydrate interactions and the initiation of the inflammatory response. Annu. Rev. Biochem. 64, 113–139 (1995).

    CAS  PubMed  Google Scholar 

  164. St Hill, C. A. Interactions between endothelial selectins and cancer cells regulate metastasis. Front. Biosci. (Landmark Ed.) 16, 3233–3251 (2011).

    CAS  Google Scholar 

  165. Genbacev, O. D. et al. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science 299, 405–408 (2003).

    CAS  PubMed  Google Scholar 

  166. Mitoma, J. et al. Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment. Nat. Immunol. 8, 409–418 (2007).

    CAS  PubMed  Google Scholar 

  167. Homeister, J. W. et al. The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing. Immunity 15, 115–126 (2001).

    CAS  PubMed  Google Scholar 

  168. Nimrichter, L. et al. Intact cell adhesion to glycan microarrays. Glycobiology 14, 197–203 (2004).

    CAS  PubMed  Google Scholar 

  169. Rabinovich, G. A., Liu, F. T., Hirashima, M. & Anderson, A. An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer. Scand. J. Immunol. 66, 143–158 (2007).

    CAS  PubMed  Google Scholar 

  170. Rabinovich, G. A. & Toscano, M. A. Turning 'sweet' on immunity: galectin–glycan interactions in immune tolerance and inflammation. Nat. Rev. Immunol. 9, 338–352 (2009).

    CAS  PubMed  Google Scholar 

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Acknowledgements

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.

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Authors and Affiliations

  1. Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK

    Evropi Theodoratou, Harry Campbell & Igor Rudan

  2. Centre for Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, Edinburgh, EH4 2XU, UK

    Nicholas T. Ventham, Nicholas A. Kennedy, Elaine Nimmo & Jack Satsangi

  3. Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1 OT Golm, Potsdam, 14476, Germany

    Daniel Kolarich

  4. Genos Ltd, Hondlova 2, Zagreb, 10000, Croatia

    Maja Pučić-Baković

  5. University of Zagreb, Faculty of Science, Horvatovac 102a, Zagreb, 10000, Croatia

    Vlatka Zoldoš

  6. Ludger Ltd, Culham Science Centre, Oxford, OX14 3EB, UK

    Daryl Fernandes

  7. IP Research Consulting SAS, 34 Rue Carnot, Paris, 93160, Noisy-le-Grand, France

    Iain K. Pemberton

  8. Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333, ZA, Netherlands

    Manfred Wuhrer

  9. Department of Medical and Surgical Specialities, Division of Gastroenterology, AOU Careggi University Hospital, Largo Brambilla 13, Florence, 50139, Italy

    Vito Annese

  10. F.Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Suite D4063, Los Angeles, 90048, CA, USA

    Dermot P. B. McGovern

  11. Department of Biochemistry and Molecular Biology, University of Zagreb Faculty of Pharmacy and Biochemistry, Trg maršala Tita 14, Zagreb, 10000, Croatia

    Gordan Lauc

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  1. Evropi Theodoratou
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Contributions

E.T. researched data, and contributed to discussion of content and writing the article. H.C., D.K., M.W., N.A.K., E.N. and J.S. contributed to the discussion of content and reviewing/editing the manuscript before submission. N.V., D.P.B.M. and G.L. contributed to writing the article and reviewing/editing it before submission. M.P.B., V.A., D.F., I.K.P., I.R. and V.Z. reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Gordan Lauc.

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Competing interests

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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