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Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome

Ripoll, VM; Pregnolato, F; Mazza, S; Bodio, C; Grossi, C; McDonnell, T; Pericleous, C; ... Giles, IP; + view all (2018) Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome. Journal of Autoimmunity 10.1016/j.jaut.2018.07.002. (In press). Green open access

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Abstract

Antiphospholipid antibodies (aPL) cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Differential mechanisms however, underlying the pathogenesis of these different manifestations of antiphospholipid syndrome (APS) are not fully understood. Therefore, we compared the effects of aPL from patients with thrombotic or obstetric APS on monocytes to identify different molecular pathways involved in the pathogenesis of APS subtypes. VT or PM IgG induced similar numbers of differentially expressed (DE) genes in monocytes. However, gene ontology (GO) analysis of DE genes revealed disease-specific genome signatures. Compared to PM, VT-IgG showed specific up regulation of genes associated with cell response to stress, regulation of MAPK signalling pathway and cell communication. In contrast, PM-IgG regulated genes involved in cell adhesion, extracellular matrix and embryonic and skeletal development. A novel gene expression analysis based on differential variability (DV) was also applied. This analysis identified similar GO categories compared to DE analysis but also uncovered novel pathways modulated solely by PM or VT-IgG. Gene expression analysis distinguished a differential effect of VT or PM-IgG upon monocytes supporting the hypothesis that they trigger distinctive physiological mechanisms. This finding contributes to our understanding of the pathology of APS and may lead to the development of different targeted therapies for VT or PM APS.

Type: Article
Title: Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jaut.2018.07.002
Publisher version: http://doi.org/10.1016/j.jaut.2018.07.002
Language: English
Additional information: Copyright © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed
Keywords: APS, Gene expression profiling, Monocytes, Pregnancy morbidity, Vascular thrombosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10053636
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