Glycoprotein A as a biomarker of pulmonary infection and inflammation in children with cystic fibrosis

Abstract

Background Serum Glycoprotein A (GlycA) levels are increased in a variety of inflammatory disease states. However, GlycA has not been previously evaluated in children with cystic fibrosis (CF). We assessed the relationship between GlycA and pulmonary infection, inflammation, bronchial wall thickening (BWT) and bronchiectasis in young children with CF. Methods From 95 patients, we obtained 311 paired serum and bronchoalveolar lavage (BAL) samples at multiple timepoints, with concurrent chest computed tomography on 168 occasions. Quantitative GlycA was determined using high‐throughput nuclear magnetic resonance metabolomic testing. Participants were considered to be infected if ≥1 significant proinflammatory organism was isolated from their BAL. The presence of free neutrophil elastase (NE) above the limit of detection was considered evidence of inflammation. The relationships between GlycA levels and infection state, inflammation, and bronchiectasis were examined using a generalized estimating equation approach. Results There was a positive relationship between GlycA (mean 1.01 mmol/L, range 0.68‐1.92 mmol/L) and being infected with one or more proinflammatory organisms, even after adjusting for age and gender (odds ratio [OR], 1.2 per 0.1 mmol/L, 95% confidence interval [CI], 1.02, 1.4, P = .03). There was also a positive relationship between GlycA and NE (unadjusted OR, 1.2 95% CI, 1.01, 1.4, P = .04), not significant after adjustment. GlycA concentration was associated with BWT but not bronchiectasis. Conclusions Although GlycA levels were higher on average in those who had an infection or neutrophilic inflammation, there was also considerable variability, limiting the clinical utility of this biomarker alone in determining early disease status in CF.

NMR Spectroscopic Windows on the Systemic Effects of SARS-CoV-2 Infection on Plasma Lipoproteins and Metabolites in Relation to Circulating Cytokines

“…Both RANTES and IP-10 (cluster 3C) are associated with inflammatory and cytotoxic T cell responses that help eliminate viruses, and their correlation with GlycA may suggest that the increase in these circulating cytokines is reflecting the severity of the respiratory infection , Neotarangelo showed that, during the course of disease, certain inflammatory markers, such as IL-6, did not change significantly, whereas others, such as soluble IL-33R (sIL-33R) and CXCL10, decreased in patients who eventually recovered but remained persistently elevated in those who succumbed to COVID-19 …”

Serum Metabolic Profiles Based on Nuclear Magnetic Resonance Spectroscopy among Patients with Deep Vein Thrombosis and Healthy Controls

“…We also found alterations in the 1 H-NMR spectral region that correspond to glycoprotein A (GlycA). Recently, glycoprotein profiles by NMR have emerged as a potential biomarker that reflects systemic inflammation in type 2 diabetes, obesity, cardiovascular events, and other pathological processes [35][36][37][38][39][40]. Levels of GlycA show an abundance of mobile N-acetyl sugar groups present on glycoproteins in circulating blood, which are involved in the acute phase response of different inflammatory disease states [40].…”

“…Recently, glycoprotein profiles by NMR have emerged as a potential biomarker that reflects systemic inflammation in type 2 diabetes, obesity, cardiovascular events, and other pathological processes [35][36][37][38][39][40]. Levels of GlycA show an abundance of mobile N-acetyl sugar groups present on glycoproteins in circulating blood, which are involved in the acute phase response of different inflammatory disease states [40]. This inflammatory biomarker could also be associated with thrombotic events and could be used as an analytic or clinical tool that may complement or provide advantages over existing clinical markers of systemic inflammation.…”

Comparison of the stability of Glycoprotein Acetyls and high sensitivity C-reactive protein as markers of chronic inflammation

“…elsewhere [38][39][40]. ALSPAC removed hsCRP values <0.15 mg/L as they were below the detection limit (0.15 mg/L) and two hsCRP measures > 80 mg/L were removed as deemed anomalies.…”