Mol. Hum. Reprod. Advance Access originally published online on May 29, 2009
Molecular Human Reproduction 2009 15(9):569-574; doi:10.1093/molehr/gap037
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GRP78 as a marker of pre-eclampsia: an exploratory study
1Laboratoire d'Hormonologie, Department of Obstetrics and Gynaecology, Maternity, University of Geneva, 32 Boulevard de la Cluse, 1211 Geneva 14, Switzerland 2Department of Anesthesiology, University of Washington Medical Center, Seattle, WA 98195-6540, USA 3Department of Anesthesia, University Hospital of Geneva, Geneva, Switzerland
4 Correspondence address. Tel: +41-22-38-24-381; Fax: +41-22-38-24-310; E-mail: marie.cohen{at}hcuge.ch
Although the exact mechanisms that lead to shallow invasion or defective trophoblastic differentiation in pre-eclampsia are still unknown, it is widely admitted that the etiology of pre-eclampsia is a defect in trophoblast invasion of the uterine spiral arteries. We have previously observed that the status of a chaperone protein, glucose regulated protein 78 (GRP78) is associated with the invasive properties of cytotrophoblastic cells; we therefore hypothesized that circulating GRP78 could serve as a diagnostic tool in pre-eclampsia. In a prospective case–control study, we quantified GRP78 autoantibodies, complexes of GRP78 with autoantibodies and GRP78 (C-term fragment, N-term fragment and full-length GRP78) by ELISA. Plasma from women diagnosed with pre-eclampsia (n = 16), from women during the first trimester of pregnancy who subsequently developed pre-eclampsia (n = 10) and from healthy pregnant women (controls, n = 58 at term, n = 26 at first trimester) were analysed and compared. We observed no significant difference between pre-eclamptic and healthy pregnant women for autoantibodies-GRP78 complexes or total GRP78 at both first trimester and at delivery. In contrast, the ratio of C-terminal GRP78 over full length GRP78 was significantly different in plasma of pre-eclamptic patients as compared with controls both during first trimester (P < 0.004) and at term (P < 0.0001). Our findings suggest that circulating C-terminal GRP78 reflect the invasive properties of cells, and could be used as a predictive marker for pre-eclampsia early in pregnancy.
Key words: GRP78/C-terminal fragment/marker/pre-eclampsia
Submitted on November 19, 2008; resubmitted on May 12, 2009; accepted on May 23, 2009.