Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Towards personalized diagnostics via longitudinal study of the human plasma N-glycome (#563)

René Hennig 1 , Samanta Cajic 2 , Udo Reichl 2 3 , Erdmann Rapp 1
  1. glyXera GmbH, Magdeburg, SACHSEN-ANHALT, Germany
  2. Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Sachsen-Anhalt, Germany
  3. Chair of Bioprocess Engineering, Otto-von-Guericke University, Magdeburg, Sachsen-Anhalt, Germany

Facilitated by substantial advances in analytical methods, plasma N-glycans have emerged as potential candidates for biomarkers. In the recent years, several investigations could link aberrant plasma N-glycosylation to numerous diseases. However, due to often limited specificity and sensitivity, only a very limited number of glycan biomarkers were approved by the authorities up to now.
The inter-individual heterogeneity of the plasma N-glycomes often mask small disease related changes in conventional large cross-sectional cohort studies, with a one-time per person sampling approach. This problem could be overcome by a longitudinal sampling approach, detecting already small changes during disease progression by monitoring the plasma N-glycome of individuals over time.
To evaluate this, we collected blood plasma samples of five healthy donors over a time period of up to six years. The plasma N-glycome was analyzed by utilizing multiplexed capillary gel electrophoresis with laser induced fluorescence detection (xCGE-LIF) as core technology [1]. By using this miniaturized electrokinetic separation technique with up to 96 capillaries in parallel, assisted by a 96-well format sample preparation and an automated data analysis by glyXtool™, a massive reduction of analysis time and costs per sample could be achieved.
We could demonstrate that the individual’s N-glycome is remarkably stable over a period of several years and free of seasonal changes. Furthermore, we could demonstrate that the inter-individual differences of the N-glycome are enormous, but by looking at the progression of the plasma N-glycome of a single person, small changes could be detected and linked to lifestyle and environmental factors. Consequently, we could show that a longitudinal sampling approach (taking time-series from individuals) can be beneficial compared to large-scale studies, where small disease related changes in the N-glycome are often hidden within the inter-individual variation of the N-glycome [2].

  1. [1] Hennig, R.; Rapp, E.; Kottler, R.; Cajic, S.; Borowiak, M.; Reichl, U.; N-Glycosylation Fingerprinting of Viral Glycoproteins by xCGE-LIF. Methods Molecular Biology (2015) 1331, 123-143.
  2. [2] Hennig, R.; Cajic, S.; Borowiak, M.; Hoffmann, M.; Kottler, R.; Reichl, U.; Rapp, E.; Towards personalized diagnostics via longitudinal study of the human plasma N-glycome. Biochimica et Biophysica Acta - General Subjects (2016) 1860, 1728-1738.