The autoimmune disease-associated transcription factors EOMES and TBX21 are dysregulated in multiple sclerosis and define a molecular subtype of disease.
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.
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
Grant P
GP
Parnell
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
Prudence N
PN
Gatt
School of Medicine, Flinders University of South Australia, South Australia 5042, Australia.
Malgorzata
M
Krupa
Department of Neurology, University of California at San Francisco, CA 94158, USA.
Dorothee
D
Nickles
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
Fiona C
FC
McKay
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
Stephen D
SD
Schibeci
Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Marcel
M
Batten
Department of Neurology, University of California at San Francisco, CA 94158, USA.
Sergio
S
Baranzini
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
Andrew
A
Henderson
Brain and Mind Research Institute, University of Sydney, Sydney, NSW 2050 Australia.
Michael
M
Barnett
School of Medicine, Flinders University of South Australia, South Australia 5042, Australia.
Mark
M
Slee
Westmead Clinical School, University of Sydney, Westmead Hospital, Sydney, New South Wales 2145, Australia.
Steve
S
Vucic
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia.
Graeme J
GJ
Stewart
Institute for Immunology and Allergy Research, Westmead Millennium Institute University of Sydney, Sydney, New South Wales 2145, Australia. Electronic address: david.booth@sydney.edu.au.
David R
DR
Booth
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000098815:T-bet Transcription Factor
C483024:CCL5 protein, human; D018946:Chemokine CCL5; C491199:EOMES protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
EOMES; Gene expression; Multiple sclerosis; TBX21; Transcription factors