Inflammatory bowel disease associates with proinflammatory potential of the immunoglobulin g glycome

IBD-BIOM Consortium, Irena Trbojević Akmačić, Nicholas T Ventham, Evropi Theodoratou, Frano Vučković, Nicholas A Kennedy, Jasminka Krištić, Elaine R Nimmo, Rahul Kalla, Hazel Drummond, Jerko Štambuk, Malcolm G Dunlop, Mislav Novokmet, Yurii Aulchenko, Olga Gornik, Harry Campbell, Maja Pučić Baković, Jack Satsangi, Gordan Lauc

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1237-47
Number of pages11
JournalInflammatory Bowel Diseases
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2015

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