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

Clin Immunol. 2016 Feb;163:96-107. doi: 10.1016/j.clim.2015.12.015. Epub 2016 Jan 4.


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.

Keywords: Biomarker; EOMES; Gene expression; MS risk gene; Multiple sclerosis; Natalizumab; TBX21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD56 Antigen
  • Case-Control Studies
  • Cell Movement
  • Dimethyl Fumarate / therapeutic use
  • Epstein-Barr Virus Nuclear Antigens / blood
  • Female
  • Fingolimod Hydrochloride / therapeutic use
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Glatiramer Acetate / therapeutic use
  • HLA-DRB1 Chains / genetics
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Interferon-beta / therapeutic use
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / genetics*
  • Natalizumab / therapeutic use
  • Polymorphism, Single Nucleotide
  • T-Box Domain Proteins / genetics*
  • Young Adult


  • CD56 Antigen
  • EOMES protein, human
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen
  • Immunologic Factors
  • Immunosuppressive Agents
  • NCAM1 protein, human
  • Natalizumab
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Glatiramer Acetate
  • Interferon-beta
  • Dimethyl Fumarate
  • Fingolimod Hydrochloride
  • EBV-encoded nuclear antigen 1