Abstract
During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. Newborns depend on maternal IgG for immune-protection in their first months. The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. A total of 37 N-glycans were quantified for IgG and 45 for the total plasma N-glycome (TPNG). The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns.
Highlights
Pregnancy induces major changes in many physiological and immunological processes[1,2]
Released glycans from purified immunoglobulin G (IgG) and total plasma from paired maternal and umbilical cord blood (UC) origin were measured by matrix-assisted laser desorption/ionisation (MALDI)-time-of-flight (TOF)-mass spectrometry (MS) (Fig. 1)
The main total plasma N-glycome (TPNG) composition H5N4E2 showed a coefficient of variation (CV) of 2.8%, while IgG-specific H4N4F1 showed a CV of 8.5%
Summary
Pregnancy induces major changes in many physiological and immunological processes[1,2]. The concentration of immunoglobulin G (IgG) – the most abundant glycoprotein in humans with an average concentration of 10.6 mg/mL – decreases during pregnancy from 9.35 mg/mL (7–17 weeks) to 7.80 mg/mL (34–38 weeks)[3] This decrease is believed to be caused by the active transfer of IgG to the developing foetus in order to establish a functional humoral immune system, as the foetus itself is only capable of producing minute amounts of IgG. Another contributing factor is dilution of plasma protein concentrations due to a 40–50% increase in plasma volume[4,5,6]. We performed the comparison using a recently developed derivatisation technique to distinguish between α2,6- and α2,3-linked sialic acids, and a high-throughput data processing package[22,23]
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