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

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

Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 163(2016) vom: 05. Feb., Seite 96-107
1. Verfasser: McKay, Fiona C (VerfasserIn)
Weitere Verfasser: Gatt, Prudence N, Fewings, Nicole, Parnell, Grant P, Schibeci, Stephen D, Basuki, Monica A I, Powell, Joseph E, Goldinger, Anita, Fabis-Pedrini, Marzena J, Kermode, Allan G, Burke, Therese, Vucic, Steve, Stewart, Graeme J, Booth, David R
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Biomarker EOMES Gene expression MS risk gene Multiple sclerosis Natalizumab TBX21 CD56 Antigen mehr... EOMES protein, human Epstein-Barr Virus Nuclear Antigens HLA-DRB1 Chains HLA-DRB1*15:01 antigen Immunologic Factors Immunosuppressive Agents NCAM1 protein, human T-Box Domain Proteins T-box transcription factor TBX21 Glatiramer Acetate 5M691HL4BO Interferon-beta 77238-31-4 Dimethyl Fumarate FO2303MNI2 Fingolimod Hydrochloride G926EC510T EBV-encoded nuclear antigen 1 O5GA75RST7
Beschreibung
Zusammenfassung:Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.
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
Beschreibung:Date Completed 28.06.2016
Date Revised 24.09.2018
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2015.12.015