Mol. Hum. Reprod. Advance Access published online on May 29, 2009
Molecular Human Reproduction, doi:10.1093/molehr/gap037
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GRP78 as a marker of preeclampsia: an exploratory study
1Department of Obstetrics and Gynaecology, Maternity, University of Geneva, Boulevard de la Cluse, 1211, Geneva 14, Switzerland 2Department of Anesthesiology, University of Washington Medical Center, Seattle, WA 98195-6540 3Department of Anesthesia, University Hospital of Geneva, Geneva, Switzerland
a To whom correspondence should be addressed: Marie Cohen, Laboratoire d'Hormonologie, 32 bd de la Cluse, 1211 Genève 14, Switzerland, 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 preeclampsia are still unknown, it is widely admitted that the etiology of preeclampsia 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 preeclampsia. 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 preeclampsia (n=16), from women during the first trimester of pregnancy who subsequently developed preeclampsia (n=10) and from healthy pregnant women (controls, n=58 at term, n=26 at first trimester) were analyzed and compared. We observed no significant difference between preeclamptic 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 preeclamptic patients as compared to 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 preeclampsia early in pregnancy.
Key Words: GRP78/C-terminal fragment/marker/preeclampsia
Submitted on November 19, 2008; resubmitted on May 12, 2009; accepted on May 23, 2009.