The autoimmune disease-associated transcription factors EOMES and TBX21 are dysregulated in multiple sclerosis and define a molecular subtype of disease

被引：47

作者：

Parnell, Grant P. ^{[1
]}

Gatt, Prudence N. ^{[1
]}

Krupa, Malgorzata ^{[2
]}

Nickles, Dorothee ^{[3
]}

McKay, Fiona C. ^{[1
]}

Schibeci, Stephen D. ^{[1
]}

Batten, Marcel ^{[4
]}

Baranzini, Sergio ^{[3
]}

Henderson, Andrew ^{[1
]}

Barnett, Michael ^{[5
]}

Slee, Mark ^{[2
]}

Vucic, Steve ^{[6
]}

Stewart, Graeme J. ^{[1
]}

Booth, David R. ^{[1
]}

机构：

[1] Univ Sydney, Inst Immunol & Allergy Res, Westmead Millennium Inst, Sydney, NSW 2145, Australia

[2] Flinders Univ South Australia, Sch Med, Bedford Pk, SA 5042, Australia

[3] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA

[4] Garvan Inst Med Res, Sydney, NSW 2010, Australia

[5] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2050, Australia

[6] Univ Sydney, Westmead Hosp, Westmead Clin Sch, Sydney, NSW 2145, Australia

来源：

CLINICAL IMMUNOLOGY | 2014年 / 151卷 / 01期

关键词：

Transcription factors; Multiple sclerosis; EOMES; TBX21; Gene expression; CHEMOKINE RECEPTORS; GENE-EXPRESSION; DOUBLE-BLIND; DISABILITY; MECHANISMS; ENCEPHALOMYELITIS; FINGOLIMOD; PATHWAYS; CELLS;

D O I：

10.1016/j.clim.2014.01.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We have identified a marked over-representation of transcription factors controlling differentiation of T, B, myeloid and NK cells among the 110 MS genes now known to be associated with multiple sclerosis (MS). To test if the expression of these genes might define molecular subtypes of MS, we interrogated their expression in blood in three independent cohorts of untreated MS (from Sydney and Adelaide) or clinically isolated syndrome (CIS, from San Francisco) patients. Expression of the transcription factors (TF) controlling T and NK cell differentiation, EOMES, TBX21 and other TFs was significantly lower in MS/CIS compared to healthy controls in all three cohorts. Expression was tightly correlated between these TFs, with other T/NK cell TFs, and to another downregulated gene, CCL5. Expression was stable over time, but did not predict disease phenotype. Optimal response to therapy might be indicated by normalization of expression of these genes in blood. (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.

引用

页码：16 / 24

页数：9

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