GlycA: Evaluation of a New Biomarker of Acute Pancreatitis

Abstract

Background: Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions, with up to 40% mortality in patients with moderate–severe AP. Glycoprotein acetylation (GlycA) is measured as a nuclear magnetic resonance signal (NMR) of the post-translational modification of glycosylated acute-phase proteins released during inflammation. We aimed to investigate the role of GlycA as an inflammatory biomarker of AP. Methods: We prospectively enrolled 20 AP patients and 22 healthy controls and collected EDTA plasma samples at admission and discharge. NMR spectra were acquired from these samples using a 400 MHz Vantera® Clinical Analyzer, and GlycA concentrations were calculated (normal = 400 μmol/L). The GlycA NMR signal, at 2.00 ± 0.01 ppm in the NMR spectrum, is derived from the N-acetyl methyl group protons within the carbohydrate side chains of circulating glycoproteins such as α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA levels were then compared between AP patients and controls, as well as within the AP group, based on etiology and severity. Results: Demographic comparisons were similar, except for a higher BMI in AP patients compared to healthy controls (29.9 vs. 24.8 kg/m2; p < 0.001). AP was mild in 10 patients, moderate in 7, and severe in 3. GlycA levels were higher in AP patients than healthy controls on admission (578 vs. 376 μmol/L, p < 0.001) and at discharge (655 vs. 376 μmol/L, p < 0.001). GlycA levels were significantly higher in patients with moderate–severe AP than in those with mild AP at discharge (533 vs. 757 μmol/L, p = 0.023) but not at admission. After adjusting for BMI, multivariable regression indicated that patients with GlycA levels > 400 μmol/L had significantly higher odds of having AP of any severity (OR = 6.88; 95% CI, 2.07–32.2; p = 0.004) and mild AP (OR = 6.12; 95% CI, 1.48–42.0; p = 0.025) than controls. Conclusion: Our pilot study highlights the use of GlycA as a novel diagnostic biomarker of inflammation in patients with AP. Our study shows that GlycA levels were significantly higher in hospitalized AP patients compared to healthy controls. Patients with moderate-to-severe AP had higher GlycA levels compared to patients with mild AP at the time of their hospital discharge, suggesting persistent inflammation in patients with severe disease.

Metabolites and lipoproteins may predict the severity of early Acute Pancreatitis in a South African cohort

“…Furthermore, GlycA was most elevated in MSAP with a slight increase in the SAP patients, suggesting increased inflammation levels in MSAP compared to MAP and SAP. Although the differences in GlycA between the groups in this study were not significantly different, it is notable that in a recent study, Shah and colleagues show that GlycA could be used as a novel diagnostic marker of inflammation in AP when compared to healthy controls (Shah et al, 2023).…”

“…Several NMR studies have shown that the integration of metabolites with meta-analysis of the transcriptome revealed a pancreatitis background in pancreatic cancer, congruent with AP being a risk factor to pancreatic cancer (Ketavarapu et al, 2022). Furthermore, 1 H-NMR metabolomics has been used to distinguish between AP patients and healthy controls or those presenting with abdominal pain (Lusczek et al, 2013; Villaseñor et al, 2014; Shah et al, 2023). In the study by Villaseñor and colleagues in 2014, the authors found changes in the lipid profile with high levels of low-density lipoprotein and unsaturated lipids, which are consistent with known disruptions in lipid metabolism in AP.…”