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

Robert Zivadinov1, Bianca Weinstock-Guttman, Marino Zorzon

  • 1Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA.

Journal of Neuroimmunology
|February 24, 2009
PubMed
Abstract

Insights

Gene-environment interactions between HLA alleles and Epstein-Barr Virus (EBV) exposure influence multiple sclerosis (MS) brain injury. Specific HLA Class I types correlate with MRI markers of disease and disability in MS patients.

Area of Science:

  • Immunogenetics
  • Neuroimmunology
  • Virology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
  • The role of Epstein-Barr Virus (EBV) infection and human leukocyte antigen (HLA) genes in MS pathogenesis is under investigation.
  • Gene-environment interactions are increasingly recognized as critical factors in complex diseases like MS.

Purpose of the Study:

  • To investigate the interplay between HLA Class I and Class II alleles and anti-EBV antibody responses.
  • To determine the association of these interactions with brain injury and clinical disability in MS patients.
  • To identify specific HLA-EBV associations with MRI-derived measures of lesion volume and brain atrophy.

Main Methods:

  • HLA typing was performed on 93 MS patients and 122 controls.
  • Antibodies against various EBV antigens (EA IgG, EBNA IgG, VCA IgM, VCA IgG) were measured.
  • Brain MRI, including T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF), was assessed.
  • Regression analysis was used to evaluate relationships between HLA alleles, anti-EBV antibodies, and clinical/MRI parameters.

Main Results:

  • HLA B7 presence was linked to increased T1-LV, higher disability (EDSS), and more severe MRI findings (higher T2-LV, lower BPF).
  • HLA B7 was also associated with a trend towards increased anti-EBV VCA IgG levels.
  • HLA A2 was associated with lower EDSS, with non-significant trends for MRI variables and anti-EBV VCA IgG.
  • The HLA B7-A2 haplotype correlated with higher T2-LV and T1-LV and a trend toward lower BPF.

Conclusions:

  • Specific HLA Class I alleles and EBV exposure demonstrate gene-environment interactions in MS.
  • These interactions are associated with key MRI markers of brain injury and atrophy in MS.
  • Findings highlight the importance of genetic background and viral exposure in MS disease progression.

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