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Article: Microvesicles and pre-eclampsia.

Sargent, Ian

2013 Volume 3, Issue 2, Page(s) 58

Abstract: The maternal syndrome of pre-eclampsia is characterised by an excessive inflammatory response associated with endothelial dysfunction, brought about by the release of multiple factors from the placenta into the maternal circulation. While some of these ... ...

Abstract	The maternal syndrome of pre-eclampsia is characterised by an excessive inflammatory response associated with endothelial dysfunction, brought about by the release of multiple factors from the placenta into the maternal circulation. While some of these factors are released as soluble molecules it is now apparent that many of them are associated with syncytiotrophoblast microvesicles and exosomes (collectively termed STBM), which are present in increased amounts in the circulation of women with pre-eclampsia. We have shown that STBM have proinflammatory, anti-endothelial and procoagulant activities in vitro, all of which are features of the maternal syndrome. We propose that the different effects of STBM result from different types of vesicles within the circulation the smaller exosomes being immunoregulatory and the larger microvesicles being proinflammatory, with a shift to the latter in pre-eclampsia. In support of this, we have demonstrated using a novel technique, Nanoparticle Tracking Analysis, that pre-eclampsia STBM are indeed larger than those from normal placentas. Furthermore, the range and types of factors they carry (and hence their functions) may differ in pre-eclampsia, where the syncytiotrophoblast is subjected to oxidative and inflammatory stress. We have carried out proteomic analysis on vesicles prepared from normal and pre-eclampsia placentas by perfusion and have identified differences in the repertoire of molecules they carry. Candidates include immunoregulatory molecules (B7-H1, CD200 and Galectin 1), complement and complement regulatory molecules (C1q, C3, CD55, CD59 and vitronectin), proinflammatory molecules (HSP70, HMGB1, Galectin 3 and Synctin 1), anti-angiogenic molecules (CD49e, CD51, CD26, Flt-1 and endoglin) and procoagulant molecules (tissue factor and phosphatidylserine). Characterising the molecular cargos of the STBM may lead to the discovery of new biomarkers for pre-eclampsia and inform future treatments.
Language	English
Publishing date	2013-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2584464-7
ISSN	2210-7797 ; 2210-7789
ISSN (online)	2210-7797
ISSN	2210-7789
DOI	10.1016/j.preghy.2013.04.004
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Article ; Conference proceedings: Pre-eclampsia – from Placenta to General Disease

Sargent, I

Zeitschrift für Geburtshilfe und Neonatologie

2009

Abstract: Pre-eclampsia is recognised clinically by its affects on the mother and baby in the second half of pregnancy, but most cases have their origin much earlier. The primary problem lies in the development of the placenta and its blood supply and is believed ... ...

Event/congress	13. Deutscher Gestose-Kongress und 11. Jenaer Geburtshilfe-Symposium, Jena, 2009
Abstract	Pre-eclampsia is recognised clinically by its affects on the mother and baby in the second half of pregnancy, but most cases have their origin much earlier. The primary problem lies in the development of the placenta and its blood supply and is believed to have an immunological cause. In particular, it involves the interaction of a unique pattern of Class I MHC molecules (HLA-C, HLA-G, HLA-E) expressed by the invasive trophoblast with highly specialised NK cells resident in the decidua. This interaction facilitates trophoblast invasion in normal pregnancy but is deficient in pre-eclampsia, leading to a poor blood supply and placental ischaemia. It is easy to understand how this directly affects the fetus but the link between the „sick“ placenta and the maternal syndrome is more challenging. It is now recognised that the maternal disease is caused by endothelial dysfunction, which itself is part of a wider systemic inflammatory response. The stimulus for this thought to have come from the placenta. A whole range of candidate placental factors have been identified in the maternal circulation and there is considerable interest in their potential as predictive markers. In particular anti-angiogenic factors such as sFlt-1 and endoglin have been the focus of much attention. However, these factors cannot explain all the features of pre-eclampsia which has led us to investigate the possible role of placental microparticles and nanoparticles in the disorder. The formation, measurement and functional activity of these particles on maternal immune and endothelial cells will be described and their potential role in pre-eclampsia discussed.
Language	English
Publishing date	2009-03-13
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	1226748-x
ISSN	1439-1651 ; 0948-2393 ; 0300-967X ; 1615-5300
ISSN (online)	1439-1651
ISSN	0948-2393 ; 0300-967X ; 1615-5300
DOI	10.1055/s-0029-1216330
Database	Thieme publisher's database

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Article: Infection in pregnancy. Report on the workshop held by the Materno-Fetal Immunology Group (MFIG) of the British Society for Immunology at the 6th Annual Congress of the BSI, December 4, 1998, in Harrogate, UK.

Sargent, I

Journal of reproductive immunology

1999 Volume 44, Issue 1-2, Page(s) 81–83

MeSH term(s)	Animals ; Coccidiosis/immunology ; Female ; Humans ; Maternal-Fetal Exchange/immunology ; Neospora/immunology ; Pregnancy ; Pregnancy Complications, Infectious/immunology ; Societies, Scientific ; Streptococcal Infections/immunology ; Streptococcus agalactiae/immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; United Kingdom
Language	English
Publishing date	1999-09
Publishing country	Ireland
Document type	Congress
ZDB-ID	424421-7
ISSN	1872-7603 ; 0165-0378
ISSN (online)	1872-7603
ISSN	0165-0378
DOI	10.1016/s0165-0378(99)00003-0
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Article ; Online: HLA-DR is aberrantly expressed at feto-maternal interface in pre-eclampsia.

Tersigni, C / Redman, C W / Dragovic, R / Tannetta, D / Scambia, G / Di Simone, N / Sargent, I / Vatish, M

Journal of reproductive immunology

2018 Volume 129, Page(s) 48–52

Abstract: In normal pregnancy, villous cytotrophoblast and syncytiotrophoblast do not express HLA Class I and Class II molecules, while invasive extravillous trophoblast only express class I HLA-C and the atypical class Ib antigens, HLA-G, -E and -F. Inadequate ... ...

Abstract	In normal pregnancy, villous cytotrophoblast and syncytiotrophoblast do not express HLA Class I and Class II molecules, while invasive extravillous trophoblast only express class I HLA-C and the atypical class Ib antigens, HLA-G, -E and -F. Inadequate maternal tolerance of invasive trophoblast has been proposed as a possible immunologic trigger of poor trophoblast invasion and subsequent occurrence of pre-eclampsia. This study aimed to investigate possible aberrant expression of class II HLA-DR on placentae and syncytiotrophoblast-derived extracellular vesicles (STEVs), obtained by dual placental perfusion, from pre-eclampsia (n = 23) and normal pregnant (n = 14) women. Here we demonstrate that HLA-DR can be detected in syncytiotrophoblast from a significant proportion of pre-eclampsia but not control placentae. HLA-DR was also observed, by flow cytometry, on STEVs and associated with placental alkaline phosphatase to validate their placental origin. HLA-DR positive syncytiotrophoblast was detected in placental biopsies from pre-eclampsia but not normal control cases, using immunohistochemistry. The HLA may be fetal or maternal origin. In the latter case a possible mechanism of acquisition is trogocytosis.
MeSH term(s)	Adult ; Extracellular Vesicles/metabolism ; Female ; Fetus/metabolism ; Flow Cytometry ; Gene Expression Regulation ; HLA-DR Antigens/genetics ; HLA-DR Antigens/metabolism ; Humans ; Immune Tolerance ; Immunohistochemistry ; Maternal-Fetal Exchange ; Placenta/immunology ; Pre-Eclampsia ; Pregnancy ; Trophoblasts/metabolism
Chemical Substances	HLA-DR Antigens
Language	English
Publishing date	2018-06-19
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424421-7
ISSN	1872-7603 ; 0165-0378
ISSN (online)	1872-7603
ISSN	0165-0378
DOI	10.1016/j.jri.2018.06.024
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Article ; Online: Placental disease and the maternal syndrome of preeclampsia: missing links?

Tannetta, Dionne / Sargent, Ian

Current hypertension reports

2013 Volume 15, Issue 6, Page(s) 590–599

Abstract: Preeclampsia remains a significant obstetric risk worldwide. The pathophysiology of preeclampsia is complex, with multiple stages involving maladaptations in both placental and maternal physiology. The placenta links the pre-clinical stage of impaired ... ...

Abstract	Preeclampsia remains a significant obstetric risk worldwide. The pathophysiology of preeclampsia is complex, with multiple stages involving maladaptations in both placental and maternal physiology. The placenta links the pre-clinical stage of impaired remodeling of the uterine vasculature, occurring in early pregnancy, to the later clinical stages characterised by the maternal syndrome of hypertension and proteinuria. This review focuses on some of the recent candidates for the missing links in this process.
MeSH term(s)	Animals ; Disease Models, Animal ; Female ; Humans ; Hypertension/physiopathology ; Placenta/blood supply ; Placenta/physiopathology ; Pre-Eclampsia/physiopathology ; Pregnancy ; Proteinuria/physiopathology
Language	English
Publishing date	2013-10-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-013-0395-7
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Zs.A 5522: Show issues

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Article: The Building Blocks of User-Focused 3D City Models

Sargent, Isabel / Holland, David / Harding, Jenny

ISPRS international journal of geo-information. 2015 Dec. 21, v. 4, no. 4

2015

Abstract: At Ordnance Survey, GB, we have taken an incremental approach to creating our 3D geospatial database. Research at Ordnance Survey has focused not only on methods for deriving 3D data, but also on the needs of the user in terms of the actual tasks they ... ...

Abstract	At Ordnance Survey, GB, we have taken an incremental approach to creating our 3D geospatial database. Research at Ordnance Survey has focused not only on methods for deriving 3D data, but also on the needs of the user in terms of the actual tasks they perform. This provides insights into the type and quality of the data required and how its quality is conveyed. In 2007, using task analysis and user-centred design, we derived a set of geometric characteristics of building exteriors that are relevant to one or more use contexts. This work has been valuable for guiding which building data to collect and how to augment our products. In 2014, we began to supply building height attributes as an alpha-release enhancement to our 2D topography data, OS MasterMap® Topography Layer. This is the first in a series of enhancements of our 2D data that forms part of a road map that will ultimately lead to a full range of 3D products. This paper outlines our research journey from the understanding of the key 3D building characteristics to the development of geo-spatial products and the specification of research. There remains a rich seam of research into methods for capturing user-focused, geo-spatial data to enable visualisation and analysis in three dimensions. Because the process of informing and designing a product is necessarily focused on the practicalities of production, storage and distribution, this paper is presented as a case report, as we believe our journey will be of interest to others involved in the capture of 3D buildings at a national level.
Keywords	buildings ; case studies ; geometry ; models ; spatial data ; surveys ; topography
Language	English
Dates of publication	2015-1221
Size	p. 2890-2904.
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2655790-3
ISSN	2220-9964
ISSN	2220-9964
DOI	10.3390/ijgi4042890
Database	NAL-Catalogue (AGRICOLA)

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Article: Does 'soluble' HLA-G really exist? Another twist to the tale.

Sargent, I L

Molecular human reproduction

2005 Volume 11, Issue 10, Page(s) 695–698

Abstract: HLA-G is thought to play a key role in implantation by modulating cytokine secretion to control trophoblast invasion and to maintain a local immunosuppressive state. It differs from other class I molecules in that the gene can be alternatively spliced to ...

Abstract	HLA-G is thought to play a key role in implantation by modulating cytokine secretion to control trophoblast invasion and to maintain a local immunosuppressive state. It differs from other class I molecules in that the gene can be alternatively spliced to produce four membrane-bound (G1, G2, G3 and G4) and three soluble isoforms (G5, G6 and G7). The soluble isoforms have recently attracted attention as their levels may be diagnostic of poor trophoblast invasion in miscarriage or pre-eclampsia and the implantation potential of IVF embryos. Although the expression and function of HLA-G2, G3, G4 and G7 has previously been a matter of debate, until now it has been generally accepted that soluble HLA-G5 and HLA-G6 are both expressed and secreted by trophoblast. However, Blaschitz et al. (2005) have reinvestigated this question and come to the surprising conclusion that they are not. They have shown that trophoblast only expresses the membrane-bound HLA-G1 isoform and not soluble HLA-G5 and -G6. Furthermore, although soluble HLA-G could be found in trophoblast culture supernatants, it appears not to be derived by alternative splicing but by the cleavage of HLA-G1. The source of the soluble HLA-G may not matter from a diagnostic perspective, but these findings, if confirmed, have important implications for our understanding of the biology of HLA-G.
MeSH term(s)	Alternative Splicing ; Biomarkers ; Embryo Implantation ; Female ; HLA Antigens/genetics ; HLA Antigens/immunology ; HLA Antigens/metabolism ; HLA-G Antigens ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/metabolism ; Humans ; Pregnancy ; Protein Isoforms/genetics ; Protein Isoforms/immunology ; Protein Isoforms/metabolism ; Protein Processing, Post-Translational ; Trophoblasts/metabolism
Chemical Substances	Biomarkers ; HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; Protein Isoforms
Language	English
Publishing date	2005-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1324348-2
ISSN	1460-2407 ; 1360-9947
ISSN (online)	1460-2407
ISSN	1360-9947
DOI	10.1093/molehr/gah196
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Article: OS045. Multi-dimensional protein identification technology analysis of syncytiotrophoblast vesicles released from perfused preeclampsia placentas.

Tannetta, D / Mackeen, M / Kessler, B / Sargent, I / Redman, C

Pregnancy hypertension

2012 Volume 2, Issue 3, Page(s) 201–202

Abstract: Introduction: In pre-eclampsia, the consequences of poor placentation lead to the second stage of pre-eclampsia, which involves activation of a maternal systemic inflammatory response (MSIR). Endothelial and other inflammatory cellular dysfunction cause ...

Abstract	Introduction: In pre-eclampsia, the consequences of poor placentation lead to the second stage of pre-eclampsia, which involves activation of a maternal systemic inflammatory response (MSIR). Endothelial and other inflammatory cellular dysfunction cause the diverse features which characterise the disorder. We have previously shown that syncytiotrophoblast microvesicles (STBM) are pro-inflammatory and circulate in increased amounts in pre-eclamptic women. We hypothesise that multiple placental "danger signals" are carried by STBM into the maternal circulation in increased amounts in PE with pro-inflammatory, anti-angiogenic and pro-coagulant activity, implicating STBM in the pathophysiology of PE. Objectives: To characterise the proteins carried by STBM from normal and PE placentas. For the first time multi-dimensional protein identification technology (MudPIT) was used to derive the proteome profiles of normal and PE placenta STBM. Methods: STBM were prepared from placentas (normal term: n=9 and PE: n=5) by dual lobe perfusion, isolated by ultracentrifugation and stored at -80°C. Normal and PE derived placenta STBM pools were then subjected to MudPIT analysis. Results: 538 proteins unique to PE STBM, 604 proteins unique to normal STBM and 1421 proteins common to both preparations were found. Preliminary analysis indicates the presence of alarmins (HSP70, and galectin 3), exosomal proteins (CD63,CD9,CD81), immunoregulatory molecules (CD26,CD200,CD47,Galectin 1), complement and complement regulatory molecules (C1q,C3,CD55,CD59 and vitronectin), amino acid transporters (CD98) and anti-angiogenic molecules (endoglin). Our analysis also reveals that proteins known to be elevated in blood before, or at, the time of pre-eclampsia are elevated or unique in STBM from PE placentas, including Fetuin A, Inter-alpha (globulin) inhibitor H4, Serum amyloid P component, Apolipoprotein H (or B2GP1) and Apolipoprotein AII. Thus, as predicted, a large number of circulating molecules are associated with STBM. The inter-relationships between proteins that are unique to either PE or normal pregnancy and the processes in which they are involved are being determined by Ingenuity Pathways Analysis software. In terms of biofunctions, preliminary analysis shows that proteins unique to PE STBM have a highly significant association (p<10(-11)) with 6 disease pathways including inflammatory, immunological, cardiovascular and reproductive system diseases and organ injury, whereas for proteins unique to normal STBM only protein synthesis was significant at the same level. Conclusion: STBM contain a heterogeneous population of vesicles that convey a large repertoire of placental proteins into the maternal circulation. The profound differences between PE and normal STBM indicate their pro-inflammatory potential.
Language	English
Publishing date	2012-06-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2584464-7
ISSN	2210-7797 ; 2210-7789
ISSN (online)	2210-7797
ISSN	2210-7789
DOI	10.1016/j.preghy.2012.04.046
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Article: Editorial.

Lyall, Fiona / Sargent, Ian

Pregnancy hypertension

2011 Volume 1, Issue 1, Page(s) 1

Language	English
Publishing date	2011-01
Publishing country	Netherlands
Document type	Editorial
ZDB-ID	2584464-7
ISSN	2210-7797 ; 2210-7789
ISSN (online)	2210-7797
ISSN	2210-7789
DOI	10.1016/j.preghy.2010.10.001
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Book ; Conference proceedings: Extracellular vesicles in health and diseases

Harrison, P. J / Gardiner, Chris / Sargent, I. L

2014

Event/congress	Microvesicles and Nanovesicles in Health and Disease (Meeting) (1st, 2010, OxfordEngland)
Author's details	edited by Paul Harrison, Chris Gardiner, Ian L. Sargent
MeSH term(s)	Transport Vesicles
Language	English
Size	xviii, 464 pages :, illustrations
Document type	Book ; Conference proceedings
ISBN	9789814411981 ; 9814411981 ; 9789814411998 ; 981441199X
Database	Catalogue of the US National Library of Medicine (NLM)

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