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

Robert Zivadinov, Bianca Weinstock-Guttman, Marino Zorzon, Laura Uxa, Maurizia Serafin, Antonio Bosco, Alessio Bratina, Cosimo Maggiore, Attilio Grop, Maria Antonietta Tommasi, Bhooma Srinivasaraghavan, Murali Ramanathan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalJournal of Neuroimmunology
Issue number1-2
Publication statusPublished - Apr 30 2009


  • Epstein-Barr virus
  • Gene-environment interactions
  • HLA
  • MHC
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology


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