title: Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Marino
authors.initials: M
authors.lastname: Zorzon
authors.forename: Laura
authors.initials: L
authors.lastname: Uxa
authors.forename: Maurizia
authors.initials: M
authors.lastname: Serafin
authors.forename: Antonio
authors.initials: A
authors.lastname: Bosco
authors.forename: Alessio
authors.initials: A
authors.lastname: Bratina
authors.forename: Cosimo
authors.initials: C
authors.lastname: Maggiore
authors.forename: Attilio
authors.initials: A
authors.lastname: Grop
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tommasi
authors.forename: Bhooma
authors.initials: B
authors.lastname: Srinivasaraghavan
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D015793:HLA-B7 Antigen / Q000235:genetics* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000821:virology; D012720:Severity of Illness Index
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D007074:Immunoglobulin G