title: HDL Glycoprotein Composition and Site-Specific Glycosylation Differentiates Between Clinical Groups and Affects IL-6 Secretion in Lipopolysaccharide-Stimulated Monocytes.
abstract: The goal of this pilot study was to determine whether HDL glycoprotein composition affects HDL's immunomodulatory function. HDL were purified from healthy controls (n = 13), subjects with metabolic syndrome (MetS) (n = 13), and diabetic hemodialysis (HD) patients (n = 24). Concentrations of HDL-bound serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), apolipoprotein A-I (ApoA-I), apolipoprotein C-III (ApoC-III), α-1-antitrypsin (A1AT), and α-2-HS-glycoprotein (A2HSG); and the site-specific glycovariations of ApoC-III, A1AT, and A2HSG were measured. Secretion of interleukin 6 (IL-6) in lipopolysaccharide-stimulated monocytes was used as a prototypical assay of HDL's immunomodulatory capacity. HDL from HD patients were enriched in SAA, LBP, ApoC-III, di-sialylated ApoC-III (ApoC-III2) and desialylated A2HSG. HDL that increased IL-6 secretion were enriched in ApoC-III, di-sialylated glycans at multiple A1AT glycosylation sites and desialylated A2HSG, and depleted in mono-sialylated ApoC-III (ApoC-III1). Subgroup analysis on HD patients who experienced an infectious hospitalization event within 60 days (HD+) (n = 12), vs. those with no event (HD-) (n = 12) showed that HDL from HD+ patients were enriched in SAA but had lower levels of sialylation across glycoproteins. Our results demonstrate that HDL glycoprotein composition, including the site-specific glycosylation, differentiate between clinical groups, correlate with HDL's immunomodulatory capacity, and may be predictive of HDL's ability to protect from infection.
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA 95816, USA.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA.
authors.forename: Romina
authors.initials: R
authors.lastname: Sacchi
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Muchena J
authors.initials: MJ
authors.lastname: Kailemia
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA 95816, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Luxardi
authors.affiliation: Biochemistry and Molecular Medicine; Internal Medicine, University of California Davis School of Medicine, Davis CA 95616, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Kaysen
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616 USA.
authors.forename: Atul N
authors.initials: AN
authors.lastname: Parikh
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616 USA.
authors.forename: Viviane N
authors.initials: VN
authors.lastname: Ngassam
authors.affiliation: Department of Medicine, University of California San Francisco, School of Medicine, San Francisco, CA 94121, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Johansen
authors.affiliation: Department of Medicine, Nephrology, Stanford School of Medicine, Stanford CA 94305, USA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Grimes
authors.affiliation: Department of Food Science &Technology, University of California, Davis, CA 95616, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Smilowitz
authors.affiliation: Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA 95816, USA.
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Zivkovic
mesh_terms: D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000276:immunology / Q000378:metabolism; D006020:Glycopeptides / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007239:Infections / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D008075:Lipoproteins, HDL / Q000302:isolation & purification / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D006435:Renal Dialysis
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006020:Glycopeptides; D006023:Glycoproteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL