Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis

J Neuroimmunol. 2009 Apr 30;209(1-2):123-30. doi: 10.1016/j.jneuroim.2009.01.023. Epub 2009 Feb 15.


Purpose: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients.

Methods: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis.

Results: The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed.

Conclusions: Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood*
  • Biomarkers / analysis
  • Biomarkers / blood
  • Brain / immunology
  • Brain / pathology*
  • Brain / virology
  • Environment
  • Female
  • Genetic Predisposition to Disease / genetics
  • HLA-A2 Antigen / genetics*
  • HLA-A2 Antigen / immunology
  • HLA-B7 Antigen / genetics*
  • HLA-B7 Antigen / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / virology
  • Severity of Illness Index


  • Antibodies, Viral
  • Biomarkers
  • HLA-A2 Antigen
  • HLA-B7 Antigen
  • Immunoglobulin G