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基于高通量 MALDI-TOF-MS 的妊娠相关血清 N-糖组学变化研究。

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

机构信息

Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Department of Rheumatology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.

出版信息

Sci Rep. 2016 Apr 14;6:23296. doi: 10.1038/srep23296.

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.

摘要

妊娠需要部分抑制免疫系统以确保母婴耐受。蛋白质糖基化,特别是末端唾液酸连接,在调节促炎和抗炎免疫反应方面至关重要。然而,关于妊娠相关的血清 N-聚糖和唾液酸连接变化知之甚少。本研究使用最近开发的方法组合,即衍生化,通过高通量 MALDI-TOF-MS 区分α2,3-和α2,6-连接的唾液酸,并通过软件辅助的数据处理,分析了 29 名健康女性在妊娠和产后 6 个时间点的血清 N-聚糖。共跟踪了 77 种 N-聚糖,部分证实了先前的发现,同时也揭示了新的关联(例如,随着分娩,FA2BG1S1(6)、FA2G1S1(6)和 A2BG2S2(6)增加)。从个体糖中,我们计算了 42 个衍生特征。用这些特征,我们观察到 α2,3-和α2,6-唾液酸化在妊娠期间增加,在分娩后减少。此外,我们还观察到三触角聚糖的α2,3-和α2,6-唾液酸化的恢复速度存在差异。总之,我们的新高通量工作流程允许识别与妊娠相关的新型血浆糖基化变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4362/4831011/6627812e4b50/srep23296-f1.jpg

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