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Clin Immunol. 2014 Mar;151(1):16-24. doi: 10.1016/j.clim.2014.01.003. Epub 2014 Jan 15.

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

Author information

  • 1Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
  • 2School of Medicine, Flinders University of South Australia, South Australia 5042, Australia.
  • 3Department of Neurology, University of California at San Francisco, CA 94158, USA.
  • 4Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
  • 5Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2050 Australia.
  • 6Westmead Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales 2145, Australia.
  • 7Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia. Electronic address: david.booth@sydney.edu.au.

Abstract

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.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

EOMES; Gene expression; Multiple sclerosis; TBX21; Transcription factors

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