The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

F.C. McKay; P.N. Gatt; N. Fewings; G.P. Parnell; S.D. Schibeci; M.A.I. Basuki; J.E. Powell; A. Goldinger; M.J. Fabis-Pedrini; A.G. Kermode; T. Burke; S. Vucic; G.J. Stewart; D.R. Booth

doi:10.1016/j.clim.2015.12.015

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The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

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The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

F.C. McKay, P.N. Gatt, N. Fewings, G.P. Parnell, S.D. Schibeci, M.A.I. Basuki, J.E. Powell, A. Goldinger, M.J. Fabis-Pedrini, A.G. Kermode, …

Clinical Immunology, Vol.163, pp.96-107

2016

DOI: https://doi.org/10.1016/j.clim.2015.12.015

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Abstract

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.

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Title: The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies
Authors/Creators: F.C. McKay (Author/Creator) - Westmead Institute for Medical Research
P.N. Gatt (Author/Creator) - Westmead Institute for Medical Research
N. Fewings (Author/Creator) - Westmead Institute for Medical Research
G.P. Parnell (Author/Creator) - Westmead Institute for Medical Research
S.D. Schibeci (Author/Creator) - Westmead Institute for Medical Research
M.A.I. Basuki (Author/Creator) - Westmead Institute for Medical Research
J.E. Powell (Author/Creator) - The University of Queensland
A. Goldinger (Author/Creator) - The University of Queensland
M.J. Fabis-Pedrini (Author/Creator) - The University of Western Australia
A.G. Kermode (Author/Creator) - Murdoch University
T. Burke (Author/Creator) - The University of Sydney
S. Vucic (Author/Creator) - The University of Sydney
G.J. Stewart (Author/Creator) - Westmead Institute for Medical Research
D.R. Booth (Author/Creator) - Westmead Institute for Medical Research
Publication Details: Clinical Immunology, Vol.163, pp.96-107
Publisher: Academic Press Inc.
Identifiers: 991005542146307891
Copyright: © 2016 Elsevier Inc
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.203 Neuromuscular Disorders; 1.203.147 Multiple Sclerosis
Web Of Science research areas: Immunology
ESI research areas: Immunology