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dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorBaecher-Allan, Clare
dc.contributor.authorMaier, Lisa M.
dc.contributor.authorArthur, Ariel T.
dc.contributor.authorOttoboni, Linda
dc.contributor.authorBarcellos, Lisa F.
dc.contributor.authorMcCauley, Jacob L.
dc.contributor.authorSawcer, Stephen
dc.contributor.authorGoris, An
dc.contributor.authorSaarela, Janna
dc.contributor.authorYelensky, Roman
dc.contributor.authorPrice, Alkes
dc.contributor.authorLeppa, Virpi
dc.contributor.authorPatterson, Nick
dc.contributor.authorde Bakker, Paul I. W.
dc.contributor.authorTran, Dong
dc.contributor.authorAubin, Cristin
dc.contributor.authorPobywajlo, Susan
dc.contributor.authorRossin, Elizabeth
dc.contributor.authorHu, Xinli
dc.contributor.authorAshley, Charles W.
dc.contributor.authorChoy, Edwin
dc.contributor.authorRioux, John D.
dc.contributor.authorPericak-Vance, Margaret A.
dc.contributor.authorIvinson, Adrian
dc.contributor.authorBooth, David R.
dc.contributor.authorStewart, Graeme J.
dc.contributor.authorPalotie, Aarno
dc.contributor.authorPeltonen, Leena
dc.contributor.authorDubois, Benedicte
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorWeiner, Howard L.
dc.contributor.authorCompston, Alastair
dc.contributor.authorHauser, Stephen L.
dc.contributor.authorDaly, Mark J.
dc.contributor.authorReich, David
dc.contributor.authorOksenberg, Jorge R.
dc.contributor.authorHafler, David A.
dc.date.accessioned2009-12-28T18:39:52Z
dc.date.available2009-12-28T18:39:52Z
dc.date.issued2009-02
dc.date.submitted2008-07
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1721.1/50257
dc.description.abstractMultiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the CD58 gene region, encoding the costimulatory molecule LFA-3, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the CD58 locus in patients with MS and control subjects. These efforts identify a CD58 variant that provides further evidence of association with MS (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the CD58 locus is captured by the rs2300747(G) allele. This protective rs2300747(G) allele is associated with a dose-dependent increase in CD58 mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced CD58 expression on circulating mononuclear cells in patients with MS is supported by finding that CD58 mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS.en
dc.description.sponsorshipNational Institutes of Healthen
dc.language.isoen_US
dc.publisherNational Academy of Sciencesen
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0813310106en
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en
dc.sourcePNASen
dc.titleThe role of the CD[subscript 5]8 locus in multiple sclerosisen
dc.typeArticleen
dc.identifier.citationDe Jager, Philip L et al. “The role of the CD58 locus in multiple sclerosis.” Proceedings of the National Academy of Sciences 106.13 (2009): 5264-5269.en
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.contributor.approverDe Jager, Philip L.
dc.contributor.mitauthorde Bakker, Paul I. W.
dc.contributor.mitauthorHafler, David A.
dc.contributor.mitauthorReich, David
dc.contributor.mitauthorDaly, Mark J.
dc.contributor.mitauthorPeltonen, Leena
dc.contributor.mitauthorPalotie, Aarno
dc.contributor.mitauthorRioux, John D.
dc.contributor.mitauthorChoy, Edwin
dc.contributor.mitauthorHu, Xinli
dc.contributor.mitauthorRossin, Elizabeth
dc.contributor.mitauthorAubin, Cristin
dc.contributor.mitauthorTran, Dong
dc.contributor.mitauthorPatterson, Nick
dc.contributor.mitauthorPrice, Alkes
dc.contributor.mitauthorOttoboni, Linda
dc.contributor.mitauthorMaier, Lisa M.
dc.contributor.mitauthorDe Jager, Philip L.
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen
dc.eprint.versionFinal published versionen
dc.identifier.pmid19237575
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
eprint.grantNumberP01 A039671en
eprint.grantNumberR01SN24247en
dspace.orderedauthorsDe Jager, P. L.; Baecher-Allan, C.; Maier, L. M.; Arthur, A. T.; Ottoboni, L.; Barcellos, L.; McCauley, J. L.; Sawcer, S.; Goris, A.; Saarela, J.; Yelensky, R.; Price, A.; Leppa, V.; Patterson, N.; de Bakker, P. I. W.; Tran, D.; Aubin, C.; Pobywajlo, S.; Rossin, E.; Hu, X.; Ashley, C. W.; Choy, E.; Rioux, J. D.; Pericak-Vance, M. A.; Ivinson, A.; Booth, D. R.; Stewart, G. J.; Palotie, A.; Peltonen, L.; Dubois, B.; Haines, J. L.; Weiner, H. L.; Compston, A.; Hauser, S. L.; Daly, M. J.; Reich, D.; Oksenberg, J. R.; Hafler, D. A.en
dc.identifier.orcidhttps://orcid.org/0000-0002-7887-4301
mit.licensePUBLISHER_POLICYen
mit.metadata.statusComplete


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