Glycosylation Failure Extends to Glycoproteins in Gestational Diabetes Mellitus

作者：Cheuk‐Lun Lee, Philip C.N. Chiu, Poh‐Choo Pang, Ivan K. Chu, Ckf Lee, Riitta Koistinen, Hannu Koistinen, Markku Seppälä, Howard R. Morris, Bérangère Tissot, Maria Panico, Anne Dell, William S.B. Yeung · 发表于：Diabetes · 年份：2011 · DOI：10.2337/db10-1186 · 被引用次数：62 · 研究领域：Reproductive System and Pregnancy、Preterm Birth and Chorioamnionitis、Gestational Diabetes Research and Management

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy. Patients with GDM are at risk for high fetal mortality and gestational complications associated with reduced immune tolerance and abnormal carbohydrate metabolism. Glycodelin-A (GdA) is an abundant decidual glycoprotein with glycosylation-dependent immunomodulatory activities. We hypothesized that aberrant carbohydrate metabolism in GDM was associated with changes in glycosylation of GdA, leading to defective immunomodulatory activities. RESEARCH DESIGN AND METHODS: GdA in the amniotic fluid from women with normal (NGdA) and GDM (DGdA) pregnancies was purified by affinity chromatography. Structural analysis of protein glycosylation was preformed by lectin-binding assay and mass spectrometry. Cytotoxicity, cell death, cytokine secretion, and GdA binding of the GdA-treated lymphocytes and natural killer (NK) cells were determined. The sialidase activity in the placental tissue from normal and GDM patients was measured. RESULTS: GDM affected the glycosylation but not the protein core of GdA. Specifically, DGdA had a lower abundance of α2-6-sialylated and high-mannose glycans and a higher abundance of glycans with Sda (NeuAcα2-3[GalNAcβ1-4]Gal) epitopes compared with NGdA. DGdA had reduced immuosuppressive activities in terms of cytotoxicity on lymphocytes, inhibitory activities on interleukin (IL)-2 secretion by lymphocytes, stimulatory activities on IL-6 secretion by NK cells, and bindin...