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* = Presenting author

P060 Inflammatory bowel disease associates with pro-inflammatory potential of the IgG glycome

I.T. Akmacic1, N. Ventham*2, E. Theodoratou3, F. Vuckovic1, N. Kennedy2, J. Kristic1, E.R. Nimmo4, R. Kalla4, H. Drummond4, J. Stambuk1, M.G. Dunlop5, M. Novokmet1, Y. Aulchenko6, O. Gornik7, I. BIOM consortium4, H. Campbell3, M. Pucic-Bakovic1, J. Satsangi4, G. Lauc1

1Genos Glycoscience Research Laboratory, Genos Glycoscience Research Laboratory, Zagreb, Croatia, 2NHS Lothian, Gastroenterology, Edinburgh, United Kingdom, 3University of Edinburgh, Centre for Population Health Sciences, Edinburgh, United Kingdom, 4University of Edinburgh, CGEM, Edinburgh, United Kingdom, 5University of Edinburgh, Colon Cancer Genetics Research Group, Edinburgh, United Kingdom, 6Novosibirsk State University, Institute of Cytology and Genetics , Novosibirsk, Russian Federation, 7University of Zagreb , Department of Biochemistry and Molecular Biology, Zagreb, Croatia

Background

Glycobiology is an underexplored research area in Inflammatory Bowel Disease (IBD), and glycans are relevant to many aetiological mechanisms described in IBD. Alterations in N-glycans attached to the 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 to 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=1.4x10-9) and significant decrease in the proportion of sialylated structures in CD (OR=0.46, CI 0.3-0.6, p=8.4x10-8).

Logistic regression models incorporating measured IgG glycan traits were able to distinguish UC and CD from controls (UC p=2.13x10-6, CD p =2.20x10-16), 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 presence to absence of bisecting GlcNAc in monogalactosylated structures was increased in patients with UC undergoing colectomy compared to no colectomy (FDR adjusted p=0.05).

Conclusion

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.