Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease

Author:

Shubhakar Archana12,Jansen Bas C1,Adams Alex T3,Reiding Karli R45,Ventham Nicholas T6,Kalla Rahul6ORCID,Bergemalm Daniel7,Urbanowicz Paulina A1,Gardner Richard A1,Wuhrer Manfred4,Wuhrer Manfred4,Halfvarson Jonas7ORCID,Satsangi Jack3,Fernandes Daryl L1,Spencer Daniel I R1ORCID,

Affiliation:

1. Ludger Ltd, Culham Science Centre , Abingdon , UK

2. Division of BioAnalytical Chemistry, VU University Amsterdam , Amsterdam , The Netherlands

3. Translational Gastroenterology Unit, University of Oxford , Oxford , UK

4. Center for Proteomics and Metabolomics, Leiden University Medical Center , Leiden , The Netherlands

5. Division of Biomolecular Mass Spectrometry and Proteomics, Utrecht University , Utrecht , The Netherlands

6. Institute of Genetics and Molecular Medicine, University of Edinburgh , Edinburgh , UK

7. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University , Örebro , Sweden

Abstract

Abstract Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52–78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54–10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.

Funder

European Commission

IBD-CHARACTER

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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