Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia
Copyright policy )Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia
Abstract Background Soluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. Methods Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. Results Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. Conclusions Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy.
- University of Cambridge United Kingdom
- King's College London, University of London
- King's College London United Kingdom
- Harris Birthright Research Centre for Fetal Medicine United Kingdom
- Birmingham Women's Hospital United Kingdom
QH471-489, LEVEL, Down’s syndrome, Endocrinology, Pre-Eclampsia, Pregnancy, Prenatal Diagnosis, BINDING, Pregnancy-Associated Plasma Protein-A, Chorionic Gonadotropin, beta Subunit, Human, Prospective Studies, Early pregnancy, Reproduction, Pregnancy Outcome, Antibodies, Monoclonal, Stillbirth, Receptors, LH, LH RECEPTOR, Fetal Diseases, LHCGR, Premature Birth, ELISA, Female, THYROID-STIMULATING HORMONE, EXPRESSION, Adult, 610, CHORIOGONADOTROPIN RECEPTOR, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, HUMAN CHORIONIC-GONADOTROPIN, Preterm delivery, Humans, Down's syndrome, Retrospective Studies, LUTEINIZING-HORMONE-RECEPTOR, Research, Reproducibility of Results, Gynecology and obstetrics, Preeclampsia, Pregnancy Trimester, First, Reproductive Medicine, CELLS, RG1-991, LIGAND, Down Syndrome, Developmental Biology
QH471-489, LEVEL, Down’s syndrome, Endocrinology, Pre-Eclampsia, Pregnancy, Prenatal Diagnosis, BINDING, Pregnancy-Associated Plasma Protein-A, Chorionic Gonadotropin, beta Subunit, Human, Prospective Studies, Early pregnancy, Reproduction, Pregnancy Outcome, Antibodies, Monoclonal, Stillbirth, Receptors, LH, LH RECEPTOR, Fetal Diseases, LHCGR, Premature Birth, ELISA, Female, THYROID-STIMULATING HORMONE, EXPRESSION, Adult, 610, CHORIOGONADOTROPIN RECEPTOR, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, HUMAN CHORIONIC-GONADOTROPIN, Preterm delivery, Humans, Down's syndrome, Retrospective Studies, LUTEINIZING-HORMONE-RECEPTOR, Research, Reproducibility of Results, Gynecology and obstetrics, Preeclampsia, Pregnancy Trimester, First, Reproductive Medicine, CELLS, RG1-991, LIGAND, Down Syndrome, Developmental Biology
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