The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies
McKay, F.C., Gatt, P.N., Fewings, N., Parnell, G.P., Schibeci, S.D., Basuki, M.A.I., Powell, J.E., Goldinger, A., Fabis-Pedrini, M.J., Kermode, A.G., Burke, T., Vucic, S., Stewart, G.J. and Booth, D.R. (2016) The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies. Clinical Immunology, 163 . pp. 96-107.
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Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p < 0.0007 for EOMES, p < 0.028 for TBX21) and demonstrate longitudinal stability (p < 10− 4) and high heritability (h2 = 0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56 + cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Publisher:||Academic Press Inc.|
|Copyright:||© 2016 Elsevier Inc|
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