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

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...

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Autores principales: Ripoll, Vera M., Pregnolato, Francesca, Mazza, Simona, Bodio, Caterina, Grossi, Claudia, McDonnell, Thomas, Pericleous, Charis, Meroni, Pier Luigi, Isenberg, David A., Rahman, Anisur, Giles, Ian P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123515/
https://www.ncbi.nlm.nih.gov/pubmed/30033000
http://dx.doi.org/10.1016/j.jaut.2018.07.002
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author Ripoll, Vera M.
Pregnolato, Francesca
Mazza, Simona
Bodio, Caterina
Grossi, Claudia
McDonnell, Thomas
Pericleous, Charis
Meroni, Pier Luigi
Isenberg, David A.
Rahman, Anisur
Giles, Ian P.
author_facet Ripoll, Vera M.
Pregnolato, Francesca
Mazza, Simona
Bodio, Caterina
Grossi, Claudia
McDonnell, Thomas
Pericleous, Charis
Meroni, Pier Luigi
Isenberg, David A.
Rahman, Anisur
Giles, Ian P.
author_sort Ripoll, Vera M.
collection PubMed
description 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.
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spelling pubmed-61235152018-09-06 Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome Ripoll, Vera M. Pregnolato, Francesca Mazza, Simona Bodio, Caterina Grossi, Claudia McDonnell, Thomas Pericleous, Charis Meroni, Pier Luigi Isenberg, David A. Rahman, Anisur Giles, Ian P. J Autoimmun Article 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. Academic Press 2018-09 /pmc/articles/PMC6123515/ /pubmed/30033000 http://dx.doi.org/10.1016/j.jaut.2018.07.002 Text en © The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ripoll, Vera M.
Pregnolato, Francesca
Mazza, Simona
Bodio, Caterina
Grossi, Claudia
McDonnell, Thomas
Pericleous, Charis
Meroni, Pier Luigi
Isenberg, David A.
Rahman, Anisur
Giles, Ian P.
Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
title Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
title_full Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
title_fullStr Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
title_full_unstemmed Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
title_short Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
title_sort gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123515/
https://www.ncbi.nlm.nih.gov/pubmed/30033000
http://dx.doi.org/10.1016/j.jaut.2018.07.002
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