Journal
CLINICAL IMMUNOLOGY
Volume 163, Issue -, Pages 96-107Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.12.015
Keywords
Multiple sclerosis; Biomarker; Gene expression; EOMES; TBX21; MS risk gene; Natalizumab
Categories
Funding
- MS Research Australia
- Trish MS Research Foundation
- NHRMC [GNT1050074, GNT 1049936]
- MS Research Australia Hunt Family Senior MS Research Fellowship
- NHMRC [GNT1046880, GNT1083405]
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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 (h(2) = 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. Crown Copyright (C) 2016 Published by Elsevier Inc. All rights reserved.
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