GlycA, a Nuclear Magnetic Resonance Spectroscopy Measure for Protein Glycosylation, is a Viable Biomarker for Disease Activity in IBD.

ABSTRACT

BACKGROUND AND AIMS: Glycoprotein acetylation [GlycA] is a novel nuclear magnetic resonance [NMR] biomarker, measured in serum or plasma, that summarizes the signals originating from glycan groups of certain acute-phase glycoproteins. This biomarker has been shown to be robustly associated with cardiovascular and short-term all-cause mortality, and with disease severity in several inflammatory conditions. We investigated GlycA levels in a cohort of healthy individuals [HCs], patients with Crohn's disease [CD] and patients with ulcerative colitis [UC] prior to and after therapeutic control of inflammation. METHODS: Serum samples of 10 HCs, 37 CD patients and 21 UC patients before and after biologic therapy were subjected to high-throughput NMR analysis by Nightingale Health Ltd. Paired C-reactive protein [CRP] and fecal calprotectin [fCal] measurements were used to characterize baseline differences, treatment effects and post-treatment association with endoscopic response [50% SES-CD decrease at Week 24] and mucosal healing [SES-CD ≤ 2 for CD, Mayo endoscopic score ≤ 1 for UC]. RESULTS: GlycA levels were significantly higher in patients with active inflammamtory bowel disease [IBD] compared with those in healthy controls, and accurately reflected the mucosal recovery to a 'healthy' state in both CD and UC patients achieving mucosal healing. In CD patients who experienced an endoscopic response without achieving full mucosal healing, GlycA levels also decreased but did not normalize to HC levels. Overall, GlycA correlated well with CRP and fCal, and accurately tracked disease activity in CRP-negative patients [<5 mg/dL]. CONCLUSION: GlycA holds promise as a viable serological biomarker for disease activity in IBD, even in patients without elevated CRP, and should therefore be tested in large prospective cohorts.