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Gastroenterology. 2018 Apr;154(5):1320-1333.e10. doi: 10.1053/j.gastro.2018.01.002. Epub 2018 Jan 6.

Glycosylation of Immunoglobulin G Associates With Clinical Features of Inflammatory Bowel Diseases.

Author information

1
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
2
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
3
Genos Glycoscience Research Laboratory, BIOCentar, Zagreb, Croatia.
4
University of Exeter, Exeter, UK.
5
Division of Gastroenterology, S. Camillo-Forlanini Hospital, Circonvallazione Gianicolense, Rome, Italy.
6
Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy.
7
Division of Gastroenterology, University Hospital, Padua, Italy.
8
Humanitas University, Inflammatory Bowel Disease Center, Department of Gastroenterology, Humanitas Clinical and Research Hospital, Milan, Italy.
9
F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
10
Division of Gastroenterology, University Hospital Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Valiant Clinic, Dubai, United Arab Emirates.
11
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; Genos Glycoscience Research Laboratory, BIOCentar, Zagreb, Croatia. Electronic address: glauc@pharma.hr.

Abstract

BACKGROUND AND AIMS:

Causes of inflammatory bowel diseases are not well understood and the most prominent forms, Crohn's disease (CD) and ulcerative colitis (UC), are sometimes hard to distinguish. Glycosylation of IgG has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. We evaluated changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups.

METHODS:

We analyzed 3441 plasma samples obtained from 2 independent cohorts of patients with CD (874 patients from Italy and 391 from the United States) or UC (1056 from Italy and 253 from the US and healthy individuals [controls]; 427 in Italy and 440 from the United States). IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry. We analyzed associations between disease status (UC vs controls, CD vs controls, and UC vs CD) and glycopeptide traits, and associations between clinical characteristics and glycopeptide traits, using a logistic regression model with age and sex included as covariates.

RESULTS:

Patients with CD or UC had lower levels of IgG galactosylation than controls. For example, the odds ratio (OR) for IgG1 galactosylation in patients with CD was 0.59 (95% confidence interval [CI], 0.51-0.69) and for patients with UC was 0.81 (95% CI, 0.71-0.92). Fucosylation of IgG was increased in patients with CD vs controls (for IgG1: OR, 1.27; 95% CI, 1.12-1.44), but decreased in patients with UC vs controls (for IgG23: OR, 0.72; 95% CI, 0.63-0.82). Decreased galactosylation associated with more severe CD or UC, including the need for surgery in patients with UC vs controls (for IgG1: OR, 0.69; 95% CI, 0.54-0.89) and in patients with CD vs controls (for IgG23: OR, 0.78; 95% CI, 0.66-0.91).

CONCLUSIONS:

In a retrospective analysis of plasma samples from patients with CD or UC, we associated levels of IgG Fc-glycosylation with disease (compared to controls) and its clinical features. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.

KEYWORDS:

Biomarker; Glycans; Glycopeptides; IBD

PMID:
29309774
PMCID:
PMC5880750
DOI:
10.1053/j.gastro.2018.01.002
[Indexed for MEDLINE]
Free PMC Article

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