Insights into the hyperglycosylation of human chorionic gonadotropin revealed by glycomics analysis

• DOI: 10.1371/journal.pone.0228507
• Publication Date: 2020-02-11T13:33:00Z
• Authors: Linda Ibeto; Aristotelis Anton...; Paola Grassi; Poh-Choo Pang; Maria Panico; Shabnam Bobdiwala; Maya Al-Memar; Paul Davis; Mark Davis; Julian Norman Taylor; Paula Almeida; Mark R. Johnson; Richard Harvey; Tom Bourne; Michael Seckl; Gary Clark; Stuart M. Haslam; Anne Dell
• Keywords: Human chorionic gonadotropin; Glycomics; Gonadotropin

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that essential for the maintenance of pregnancy. Glycosylation hCG known to be its biological activity. “Hyperglycosylated” variants secreted during early pregnancy have been proposed involved in initial implantation embryo and as potential diagnostic marker gestational diseases. However, what constitutes “hyperglycosylation” not yet fully understood. In this study, we perform comparative N-glycomic analysis expressed same individuals late help provide new insights into function, reveal targets diagnostics clarify identity hyperglycosylated hCG. was isolated urine collected from women at 7 weeks 20 weeks’ gestation. also diagnosed with trophoblastic disease (GTD). We used glycomics methodologies including matrix assisted laser desorption/ionisation–time flight (MALDI-TOF) mass spectrometry (MS) MS/MS methods characterise N-glycans associated purified individual samples. The structures identified on (EP-hCG) (LP-hCG) samples corresponded mono-, bi-, tri-, tetra-antennary N-glycans. A novel finding presence substantial amounts bisected type samples, which were present much lower levels GTD second observation abundant LewisX antigens GTD-hCG had fewer glycoforms constituted subset those found normal When compared EP-hCG, decreased signals tri- terms terminal epitopes, increased sialylated structures, while very minor abundance. carries throughout but different proportions. N-glycan repertoire more diverse than previously reported. Bisected are diagnostics. inhibits NK cell cytotoxicity vitro nanomolar glycans implicated suppression cytotoxicity, suggesting hCG-related may directly suppress cytotoxicity.