Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease
Shubhakar A., Jansen BC., Adams AT., Reiding KR., Ventham NT., Kalla R., Bergemalm D., Urbanowicz PA., Gardner RA., Wuhrer M., Halfvarson J., Satsangi J., Fernandes DL., Spencer DIR.
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. Forty-seven 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 a 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 personalized medicine in IBD.