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dc.contributor.authorS. Gandhi, Kaushalen_US
dc.contributor.authorC. McKay, Fionaen_US
dc.contributor.authorCox, Matthewen_US
dc.contributor.authorRiveros, Carlosen_US
dc.contributor.authorArmstrong, Nicolaen_US
dc.contributor.authorN. Heard, Roberten_US
dc.contributor.authorVucic, Steveen_US
dc.contributor.authorW. Williams, Daviden_US
dc.contributor.authorStankovich, Jimen_US
dc.contributor.authorBrown, Matthewen_US
dc.contributor.authorDanoy, Patricken_US
dc.contributor.authorJ. Stewart, Graemeen_US
dc.contributor.authorBroadley, Simonen_US
dc.contributor.authorMoscato, Pabloen_US
dc.contributor.authorLechner-Scott, Jeannetteen_US
dc.contributor.authorJ. Scott, Rodneyen_US
dc.contributor.authorR. Booth, Daviden_US
dc.contributor.authorGriffiths, Lynen_US
dc.contributor.authoral, eten_US
dc.contributor.editorKay Davies, Anthony Wynshaw-Boris, Joel Hirschhornen_US
dc.description.abstractMultiple sclerosis (MS) is an autoimmune disease with a genetic component, caused at least in part by aberrant lymphocyte activity. The whole blood mRNA transcriptome was measured for 99 untreated MS patients: 43 primary progressive MS, 20 secondary progressive MS, 36 relapsing remitting MS and 45 age-matched healthy controls. The ANZgene Multiple Sclerosis Genetics Consortium genotyped more than 300 000 SNPs for 115 of these samples. Transcription from genes on translational regulation, oxidative phosphorylation, immune synapse and antigen presentation pathways was markedly increased in all forms of MS. Expression of genes tagging T cells was also upregulated (P < 10212) in MS. A T cell gene signature predicts disease state with a concordance index of 0.79 with age and gender as co-variables, but the signature is not associated with clinical course or disability. The ANZgene genome wide association screen identified two novel regions with genome wide significance: one encoding the T cell co-stimulatory molecule, CD40; the other a region on chromosome 12q13-14. The CD40 haplotype associated with increased MS susceptibility has decreased gene expression in MS (P < 0.0007). The second MS susceptibility region includes 17 genes on 12q13-14 in tight linkage disequilibrium. Of these, only 13 are expressed in leukocytes, and of these the expression of one, FAM119B, is much lower in the susceptibility haplotype (P < 10214). Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS.en_US
dc.publisherOxford University Pressen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofjournalHuman Molecular Geneticsen_US
dc.subject.fieldofresearchNeurology and Neuromuscular Diseasesen_US
dc.titleThe Multiple Sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesisen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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