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Abstract / Description of output
Human plasma transferrin (Tf) N-glycosylation has been mostly studied as a marker for congenital disorders of glycosylation, alcohol abuse, and hepatocellular carcinoma. However, inter-individual variability of Tf N-glycosylation is not known, mainly due to technical limitations of Tf isolation in large-scale studies. Here, we present a highly specific robust high-throughput approach for Tf purification from human blood plasma and detailed characterization of Tf N-glycosylation on the level of released glycans by ultra-high-performance liquid chromatography based on hydrophilic interactions and fluorescence detection (HILIC-UHPLC-FLD), exoglycosidase sequencing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We perform a large-scale comparative study of Tf and immunoglobulin G (IgG) N-glycosylation analysis in two human populations and demonstrate that Tf N-glycosylation is associated with age and sex, along with multiple biochemical and physiological traits. Observed association patterns differ compared to the IgG N-glycome corroborating tissue-specific N-glycosylation and specific N-glycans' role in their distinct physiological functions.
Original language | English |
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Article number | 312 |
Number of pages | 13 |
Journal | Communications Biology |
Volume | 6 |
Issue number | 1 |
DOIs | |
Publication status | Published - 23 Mar 2023 |
Keywords / Materials (for Non-textual outputs)
- Humans
- Glycosylation
- High-Throughput Screening Assays
- Immunoglobulin G/blood
- Protein Processing, Post-Translational
- Transferrin/chemistry
- Polysaccharides/analysis
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- 1 Finished
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Determining the causal links and clinical significance of rare genetic variants
12/02/18 → 11/02/21
Project: Research