title: HtrA3 Isoform-Specific ELISAs for Early Detection of Preeclampsia.
abstract: Preeclampsia is a serious disorder of human pregnancy occurring after 20 weeks of gestation. It can be divided into subtypes of early onset (<34 weeks of gestation) and late onset (>34 weeks). Presymptomatic detection to identify those at high risk is important for managing this disease. HtrA3, a serine protease with high expression in the developing placenta, exists in long (HtrA3-L) and short (HtrA3-S) isoforms. They are identical, except HtrA3-S lacks the C-terminal PDZ domain. We have previously shown by Western blot analysis that serum HtrA3 levels at the end of the first trimester are significantly higher in women who later develop preeclampsia than in controls. In this study, using highly specific HtrA3 monoclonal antibodies, we established and fully validated two enzyme-linked immunosorbent assays to detect both HtrA3 isoforms together (HtrA3-T) and HtrA3-L alone in the human serum. We then determined serum HtrA3 at 11 to 13 weeks of gestation in a cohort of singleton pregnancies that proceeded without complications or developed preeclampsia in the third trimester. Compared with controls, those who developed late-onset preeclampsia had significantly higher levels of HtrA3-L, whereas those who developed early-onset preeclampsia had significantly lower ratios of HtrA3-L/HtrA3-T. These data support a potential utility of these HtrA3 ELISAs for early detection of preeclampsia.
authors.affiliation: 1 Implantation and Placental Development Laboratory, Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|2 Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1 Implantation and Placental Development Laboratory, Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|2 Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: 3 Central Clinical School, University of Sydney, Sydney, NSW, Australia.|4 RPA Women and Babies, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hyett
authors.affiliation: 5 Monash Ultrasound for Women, Melbourne, VIC, Australia.|6 Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
authors.forename: Fabricio
authors.initials: F
authors.lastname: da Silva Costa
authors.affiliation: 1 Implantation and Placental Development Laboratory, Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|2 Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia.|7 Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Guiying
authors.initials: G
authors.lastname: Nie
mesh_terms: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D019921:Biotinylation; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000097:blood / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D020033:Protein Isoforms; C474013:HTRA3 protein, human; D012697:Serine Endopeptidases
keywords: HtrA3; early detection; isoform; preeclampsia; preeclampsia subtypes