Abstract
Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy.
Highlights
Various changes in the glycosylation of serum proteins, including IgG and α 1-antitrypsin (AAT), have been observed during pregnancy[3,12,13]
A different technique extensively used for high-throughput profiling is MALDI-TOF-MS, which allows for the acquisition of a glycan spectrum within seconds, while LC based methods generally require much more time[23,24]
A set of 77 N-glycan compositions were consistently detected and quantified in the glycan profiles acquired by MALDI-TOF-MS (Supplementary Table S2), from which 42 derived traits were calculated based on the compositional features (Supplementary Table S3)
Summary
Various changes in the glycosylation of serum proteins, including IgG and α 1-antitrypsin (AAT), have been observed during pregnancy[3,12,13]. Technical challenges posed by the instability and ionization bias observed for sialylated glycans have been successfully overcome by permethylation as well as by selective stabilisation of sialic acids by e.g. ethyl esterification[25,26,27,28,29,30]. The latter method introduces a mass difference between α 2,3- and an α 2,6-linked sialic acids, allowing their discrimination by mass spectrometry, and is well suited for high-throughput N-glycan profiling using MALDI-TOF-MS27. MassyTools calculates a wide variety of spectral and analyte quality criteria that allow for an efficient and reliable automated curation of (clinical) data
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