Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS

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.

The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation

“…Human plasma protein N-glycosylation is an extensive area of research, with detailed descriptions of the abundance of each glycan, identification of proteins harboring each glycan, and how these glycans affect protein function (36). The plasma N-glycome is increasingly explored as a potential biomarker in a variety of settings including depression (52-54), pregnancy (55), IBD (56), Down syndrome (57), inflammation and metabolic health (58), and post-surgical changes (59). Given the repeated association of SLC39A8 with glycosylation defects in prior studies (25)(26)(27)(28)38), and the exquisite sensitivity of certain glycosyltransferases for Mn as an irreplaceable co-factor, we focused our study on glycosylation changes in A391T carriers.…”

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

“…Interestingly, in a study analyzing the total N-serum glycome during and after pregnancy, both α2,3and α2,6-linked sialylation were found to increase during pregnancy. 35,36 In our study, 21 cases of CDG with NIHF were reviewed. All the NIHF were reported prenatally or present at birth.…”

Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health

“…Although similarly sized investigations have analyzed plasma N-glycosylation by separation techniques like (U) HPLC or CGE-LIF (18 -20, 23, 70), to our knowledge this is the largest study of its kind performed by MS (32)(33)(34). Glycan compositions as obtained by MS provide orthogonal information to chromatographic peaks.…”

“…Mass spectrometry provides orthogonal information from these methodologies, as it does not distinguish isomers but instead unambiguously evaluates glycans on a compositional level (29 -31). To date, a large mass spectrometric TPNG study remains to be performed for revealing associations with markers of inflammation and metabolic health (32)(33)(34).…”