HLA class II is aberrantly expressed on circulating syncytiotrophoblast microparticles in early onset pre-eclampsia

Abstract

s / Placenta 36 (2015) A1eA60 A7 NI3.3. HLA CLASS II IS ABERRANTLY EXPRESSED ON CIRCULATING SYNCYTIOTROPHOBLAST MICROPARTICLES IN EARLY ONSET PREECLAMPSIA Chiara Tersigni , Christopher Redman , Dionne Tannetta , Rebecca Dragovic , Sylvia Shahjahan , Nicoletta Di Simone , Ian Sargent , Manu Vatish . Department of Obstetrics and Gynaecology, Universit a Cattolica del Sacro Cuore, Policlinico A. Gemelli, 00168, Rome, Italy; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women’s Centre, John Radcliffe Hospital, OX3 9DU, Oxford, UK Objectives: The lack of expression of major histocompatibility complex (MHC) class II in trophoblast tissues is believed to be one of the escape mechanisms of the fetus from maternal immune system. Since an exaggerate systemic inflammatory response is known to be a feature of pre-eclampsia (PET), aim of this study was to investigate the possible abnormal expression of MHC class II molecules, namely HLA-DR, in circulating syncytiotrophoblast microparticles (STBMs) from preeclamptic patients. Methods: STBMs obtained by dual placental perfusion after caesarean section from 9 women with early onset ( 34 weeks of gestation) PET (EOPET), 7 women with late onset (>34 weeks of gestation) PET (LOPET) and 12 women with uncomplicated pregnancies were analysed for HLADR and the syncytiotrophoblast-specific placental alkaline phosphatase (PLAP) expression by flow cytometry. Results: STBMs from women with EOPET showed a significant expression of HLA-DR coupled with PLAP compared to controls (P1⁄40.03). No significant difference was found between either controls and LOPET (P1⁄40.24) or EOPET and LOPET (P1⁄40.35) (Figure 1). Figure 1. Percentage of STBMs double positivity for HLA-DR and PLAP obtained from uncomplicated pregnancies (controls), women with EOPET or LOPET. A significant aberrant expression of HLA-DR was found in EOPET women compared to controls (*P1⁄40.03). Conclusion: To our knowledge, this is the first observation of an aberrant expression of HLA-DR in STBMs from women with EOPET. This finding might lead the way to the identification of a novel immunological mechanism representing a co-cause or a consequence of the exaggerate pro-inflammatory status that is a feature of PET. More studies are needed to confirm this observation in a larger cohort of patients and to define the possible functional role of aberrant HLA-DR expressed on STBMs spread in maternal circulation in PET. NI3.4. AN INTEGRATED TRANSCRIPTIONAL, EPIGENETIC, AND CLINICAL ANALYSIS OF PREECLAMPTIC PLACENTAS Katherine Leavey , Samantha Wilson , Shannon Bainbridge , Wendy Robinson , Brian Cox . University of Toronto, Toronto, Ontario, Canada; University of British Columbia, Vancouver, British Columbia, Canada; University of Ottawa, Ottawa, Ontario, Canada Objectives: Preeclampsia (PE) is a complex, multi-system disorder of pregnancy, demonstrating a high degree of variability in observed maternal symptoms and fetal outcomes. We hypothesize that this heterogeneity, leading to a lack of robust predictive biomarkers and effective treatments for this disorder, is due to the existence of multiple molecular forms of PE. While transcriptional analysis of placenta samples can group and classify patients, the integration of epigenetic information should reveal gene regulatory mechanisms behind the pathology. Methods: To address our hypothesis, microarray gene expression data was collected for 330 placentas, including 157 highly annotated samples drawn from the RCWIH BioBank. This combined data set was then subjected to unsupervised model-based clustering and correlative analysis with the available clinical covariates. Additionally, 48 BioBank samples were further assessed by methylation arrays, and genes differentially methylated and/or expressed between clusters were investigated by pathway enrichment analysis. Results: Clustering of the transcriptional data revealed four subclasses of PE samples, including a group with relatively healthy placentas, normal birth weights, and term deliveries, indicating a possible maternal origin of the pathology. An identified “canonical” PE subclass, with clinical presentation of low placental weights and early deliveries, was associated with hypo-methylation and increased expression of genes related to secretion, metabolism, and response to hypoxia, including known PE markers ENG, INHA, and LEP. The third PE group demonstrated severe fetal growth restriction and hypo-methylation of genes involved in immune response, while the fourth subclass formed due to chromosomal abnormalities, confirmed by aCGH analysis, leading to cohesive changes in gene expression but not in methylation status. Conclusion: Overall, our integrated molecular and clinical analysis of preeclamptic placentas has identified multiple subtypes of this disorder, fitting with our hypothesis. Hopefully, this research will eventually lead to the development of robust biomarkers and personalized treatments for all PE subclasses. NI3.5. INTEGRATIVE ANALYSIS OF PLACENTAL TRANSCRIPTOME ORGANIZATION REVEALS HIGHLY CONSERVED REGULATORY PROGRAMS AND POINTS TOWARD A PREECLAMPSIA GENE CLUSTER Sam Buckberry , Tina Bianco-Miotto , Stephen Bent , Gustaaf Dekker , Claire Roberts . 1 The Robinson Research Institute, The University of Adelaide, SA, Australia; 2 School of Agriculture, Food & Wine, The University of Adelaide, SA, Australia; 3 Lyell McEwin Hospital, SA,