title: Inflammatory bowel disease associates with proinflammatory potential of the immunoglobulin G glycome.
abstract: BACKGROUND
  Glycobiology is an underexplored research area in inflammatory bowel disease (IBD), and glycans are relevant to many etiological mechanisms described in IBD. Alterations in N-glycans attached to the immunoglobulin G (IgG) Fc fragment can affect molecular structure and immunological function. Recent genome-wide association studies reveal pleiotropy between IBD and IgG glycosylation. This study aims to explore IgG glycan changes in ulcerative colitis (UC) and Crohn's disease (CD).
  
  
  METHODS
  IgG glycome composition in patients with UC (n = 507), CD (n = 287), and controls (n = 320) was analyzed by ultra performance liquid chromatography.
  
  
  RESULTS
  Statistically significant differences in IgG glycome composition between patients with UC or CD, compared with controls, were observed. Both UC and CD were associated with significantly decreased IgG galactosylation (digalactosylation, UC: odds ratio [OR] = 0.71; 95% confidence interval [CI], 0.5-0.9; P = 0.01; CD: OR = 0.41; CI, 0.3-0.6; P = 1.4 × 10) and significant decrease in the proportion of sialylated structures in CD (OR = 0.46, CI, 0.3-0.6, P = 8.4 × 10). Logistic regression models incorporating measured IgG glycan traits were able to distinguish UC and CD from controls (UC: P = 2.13 × 10 and CD: P = 2.20 × 10), with receiver-operator characteristic curves demonstrating better performance of the CD model (area under curve [AUC] = 0.77) over the UC model (AUC = 0.72) (P = 0.026). The ratio of the presence to absence of bisecting GlcNAc in monogalactosylated structures was increased in patients with UC undergoing colectomy compared with no colectomy (FDR-adjusted, P = 0.05).
  
  
  CONCLUSIONS
  The observed differences indicate significantly increased inflammatory potential of IgG in IBD. Changes in IgG glycosylation may contribute to IBD pathogenesis and could alter monoclonal antibody therapeutic efficacy. IgG glycan profiles have translational potential as IBD biomarkers.
authors.affiliation: *Genos Glycoscience Research Laboratory, Zagreb, Croatia; †Gastrointestinal Unit, Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; ‡Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom; §Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, United Kingdom; ‖Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; ¶Novosibirsk State University, Novosibirsk, Russia; and **Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Irena
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authors.lastname: Trbojević Akmačić
authors.forename: Nicholas T
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authors.lastname: Ventham
authors.forename: Evropi
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authors.lastname: Theodoratou
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authors.lastname: Kennedy
authors.forename: Jasminka
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authors.lastname: Krištić
authors.forename: Elaine R
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authors.lastname: Nimmo
authors.forename: Rahul
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authors.lastname: Kalla
authors.forename: Hazel
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authors.lastname: Drummond
authors.forename: Jerko
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authors.lastname: Štambuk
authors.forename: Malcolm G
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authors.lastname: Dunlop
authors.forename: Mislav
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authors.lastname: Novokmet
authors.forename: Yurii
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authors.lastname: Aulchenko
authors.forename: Olga
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authors.lastname: Gornik
authors.forename: Harry
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authors.lastname: Campbell
authors.forename: Maja
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authors.lastname: Pučić Baković
authors.forename: Jack
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authors.lastname: Satsangi
authors.forename: Gordan
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authors.lastname: Lauc
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011134:Polysaccharides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012372:ROC Curve; D006023:Glycoproteins
chemical_list: D007074:Immunoglobulin G; D011134:Polysaccharides; C046179:glycosylated IgG; D006023:Glycoproteins