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

Grant Parnell, Prudence Gatt, Malgorzata Krupa, Dorothee Nickles, Fiona McKay, Stephen Schibeci, Marcel Batten, Sergio Baranzini, Andrew Henderson, Michael Barnett, Mark Slee, Steve Vucic, Graeme Stewart, David Booth

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)16-24
    Number of pages9
    JournalClinical Immunology
    Volume151
    Issue number1
    DOIs
    Publication statusPublished - 2014

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