The autoimmune disease-associated transcription factors EOMES and TBX21 are dysregulated in multiple sclerosis and define a molecular subtype of disease
Copyright policy )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.
- University of California, San Francisco United States
- University of Sydney Australia
- Flinders University Australia
- Garvan Institute of Medical Research Australia
- University of California San Francisco United States
Adult, Male, Multiple Sclerosis, Adolescent, T-Lymphocytes, Immunology, Multiple sclerosis, Cohort Studies, Transcription factors, Immunology and Allergy, Humans, T-bet Transcription Factor, Chemokine CCL5, Aged, B-Lymphocytes, Gene Expression Profiling, Cell Differentiation, Middle Aged, TBX21, Killer Cells, Natural, Gene Expression Regulation, Case-Control Studies, EOMES, Female, Gene expression, T-Box Domain Proteins, Signal Transduction
Adult, Male, Multiple Sclerosis, Adolescent, T-Lymphocytes, Immunology, Multiple sclerosis, Cohort Studies, Transcription factors, Immunology and Allergy, Humans, T-bet Transcription Factor, Chemokine CCL5, Aged, B-Lymphocytes, Gene Expression Profiling, Cell Differentiation, Middle Aged, TBX21, Killer Cells, Natural, Gene Expression Regulation, Case-Control Studies, EOMES, Female, Gene expression, T-Box Domain Proteins, Signal Transduction
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