engleski

Associations between plasma protein, IgG and IgA N-glycosylation and metabolic health markers in pregnancy and gestational diabetes

Background Monitoring human circulating N-glycome could provide valuable insight into an individual’s metabolic status. Therefore, we examined if aberrant carbohydrate metabolism in gestational diabetes mellitus (GDM) associates with alterations in plasma protein, immunoglobulin G (IgG) and immunoglobulin A (IgA) N-glycosylation. Methods Plasma protein, IgG and IgA N-glycans were enzymatically released, purified and chromatographically profiled in 48 pregnant women with normal glucose tolerance and 41 pregnant women with GDM, all sampled at 24–28 weeks of gestation. Linear mixed models adjusting for age and multiple testing (FDR<0.05) were used to investigate the associations between glycosylation features, metabolic markers and GDM status. Results Fasting insulin exhibited significant associations to numerous glycan traits, including plasma protein galactosylation, sialylation, branching, core fucosylation and bisection, to IgG core fucosylated, bisected (FA2B) and afucosylated disialylated (A2G2S2) glycan and to IgA trisialylated triantennary (A3G3S3) glycan (padj range: 4.37x10-05–4.94x10-02). Insulin resistance markers HOMA2-IR and HOMA2-%B were mostly associated to the same glycan structures as fasting insulin. Both markers showed positive association with high-branched plasma glycans (padj = 1.12x10-02 and 2.03x10-03) and negative association with lowbranched plasma glycans (padj = 1.21x10-02 and 2.05x10-03). Additionally, HOMA2-%B index was significantly correlated with glycosylation features describing IgG sialylation. Multiple plasma protein IgG and IgA glycans showed significant associations with total PLOS ONE PLOS ONE | https://doi.org/10.1371/journal.pone.0284838 April 20, 2023 1 / 17 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Sˇtambuk T, Kifer D, Smirčić-Duvnjak L, Vučić Lovrenčić M, Gornik O (2023) Associations between plasma protein, IgG and IgA Nglycosylation and metabolic health markers in pregnancy and gestational diabetes. PLoS ONE 18(4): e0284838. https://doi.org/10.1371/journal. pone.0284838 Editor: Alok Raghav, Gachon University Gil Medical Center, DEMOCRATIC PEOPLE’S REPUBLIC OF KOREA Received: June 1, 2022 Accepted: April 11, 2023 Published: April 20, 2023 Copyright: © 2023 Sˇtambuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting information files. Funding: This work was supported by: 1) European Structural and Investments funding for the “Croatian National Centre of Research Excellence in Personalized Healthcare”, OG, [contract #KK.01.1.1.01.0010], https://www.zci.hr/en/ http:// zcipersonhealth.unios.hr/en 2)European Regional cholesterol and triglyceride levels. None of the tested glycan traits showed a significant difference between GDM and normoglycemic pregnancies. Conclusion Markers of glucose homeostasis and lipid metabolism in pregnancy show extensive associations to various N-glycosylation features. However, plasma protein, IgG and IgA N-glycans were not able to differentiate pregnant women with and without GDM, possibly due to numerous physiological changes accompanying pregnancy, which confound the impact of GDM on protein glycosylation.

N-glycosylation, gestational diabetes, IgA, IgG

nije evidentirano