Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.

<h4>Background</h4>Although the most common clinical presentation of multiple sclerosis (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has...

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Autores principales:	Haritz Irizar, Maider Muñoz-Culla, Lucia Sepúlveda, Matías Sáenz-Cuesta, Álvaro Prada, Tamara Castillo-Triviño, Gorka Zamora-López, Adolfo López de Munain, Javier Olascoaga, David Otaegui
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2133bec604e4dd4b70987c1528b51d9
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spelling	oai:doaj.org-article:f2133bec604e4dd4b70987c1528b51d92021-11-18T08:30:17ZTranscriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.1932-620310.1371/journal.pone.0090482https://doaj.org/article/f2133bec604e4dd4b70987c1528b51d92014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587374/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Although the most common clinical presentation of multiple sclerosis (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMS patients.<h4>Results</h4>The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 patients in remission and relapse and 25 healthy subjects has revealed 174 genes altered in both remission and relapse, a high proportion of them showing what we have called "mirror pattern": they are upregulated in remission and downregulated in relapse or vice versa. The coexpression analysis of these genes has shown that they are organized in three female-specific and one male-specific modules.<h4>Conclusions</h4>The interpretation of the modules of the coexpression network suggests that Epstein-Barr virus (EBV) reactivation of B cells happens in MS relapses; however, qPCR expression data of the viral genes supports that hypothesis only in female patients, reinforcing the notion that different molecular processes drive disease progression in females and males. Besides, we propose that the "primed" state showed by neutrophils in women is an endogenous control mechanism triggered to keep EBV reactivation under control through vitamin B12 physiology. Finally, our results also point towards an important sex-specific role of non-coding RNA in MS.Haritz IrizarMaider Muñoz-CullaLucia SepúlvedaMatías Sáenz-CuestaÁlvaro PradaTamara Castillo-TriviñoGorka Zamora-LópezAdolfo López de MunainJavier OlascoagaDavid OtaeguiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e90482 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Haritz Irizar Maider Muñoz-Culla Lucia Sepúlveda Matías Sáenz-Cuesta Álvaro Prada Tamara Castillo-Triviño Gorka Zamora-López Adolfo López de Munain Javier Olascoaga David Otaegui Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
description	<h4>Background</h4>Although the most common clinical presentation of multiple sclerosis (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMS patients.<h4>Results</h4>The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 patients in remission and relapse and 25 healthy subjects has revealed 174 genes altered in both remission and relapse, a high proportion of them showing what we have called "mirror pattern": they are upregulated in remission and downregulated in relapse or vice versa. The coexpression analysis of these genes has shown that they are organized in three female-specific and one male-specific modules.<h4>Conclusions</h4>The interpretation of the modules of the coexpression network suggests that Epstein-Barr virus (EBV) reactivation of B cells happens in MS relapses; however, qPCR expression data of the viral genes supports that hypothesis only in female patients, reinforcing the notion that different molecular processes drive disease progression in females and males. Besides, we propose that the "primed" state showed by neutrophils in women is an endogenous control mechanism triggered to keep EBV reactivation under control through vitamin B12 physiology. Finally, our results also point towards an important sex-specific role of non-coding RNA in MS.
format	article
author	Haritz Irizar Maider Muñoz-Culla Lucia Sepúlveda Matías Sáenz-Cuesta Álvaro Prada Tamara Castillo-Triviño Gorka Zamora-López Adolfo López de Munain Javier Olascoaga David Otaegui
author_facet	Haritz Irizar Maider Muñoz-Culla Lucia Sepúlveda Matías Sáenz-Cuesta Álvaro Prada Tamara Castillo-Triviño Gorka Zamora-López Adolfo López de Munain Javier Olascoaga David Otaegui
author_sort	Haritz Irizar
title	Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
title_short	Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
title_full	Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
title_fullStr	Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
title_full_unstemmed	Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
title_sort	transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f2133bec604e4dd4b70987c1528b51d9
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Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.

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