title: GRP78 as a marker of pre-eclampsia: an exploratory study.
abstract: 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.
authors.affiliation: Laboratoire d'Hormonologie, Department of Obstetrics and Gynaecology, Maternity, University of Geneva, 1211 Geneva 14, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Laverrière
authors.forename: R
authors.initials: R
authors.lastname: Landau
authors.forename: I
authors.initials: I
authors.lastname: Charvet
authors.forename: O
authors.initials: O
authors.lastname: Irion
authors.forename: P
authors.initials: P
authors.lastname: Bischof
authors.forename: M
authors.initials: M
authors.lastname: Morales
authors.forename: M
authors.initials: M
authors.lastname: Cohen
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005865:Gestational Age; D006360:Heat-Shock Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins