title: Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk.
abstract: BACKGROUND
  Risk factors for multiple sclerosis (MS) include human leukocyte antigen (HLA)-DR and Epstein-Barr virus (EBV)-specific antibody responses, including an epitope within EBV nuclear antigen 1 (EBNA-1) that is of recent interest.
  
  
  OBJECTIVE
  The objective of this paper is to assess case-control associations between MS risk and anti-EBV antibody levels as well as HLA-DR profiles, gender and age in a population-based cohort.
  
  
  METHODS
  Serological responses to EBV were measured in 426 MS patients and 186 healthy controls. HLA-DR typing was performed using sequence-based methods.
  
  
  RESULTS
  MS patients had significantly higher levels of antibodies against epitope-specific and polyspecific EBNA-1 and viral capsid antigen (VCA), compared with controls (all p < 10(-15)). In regression analyses, anti-EBNA-1 and anti-VCA antibody levels, protective HLA-DR*04/07/09 alleles and gender (all p < 0.003) contributed independently to a model that classified cases and controls with an odds ratio > 20 (sensitivity 92%, specificity 64%). Notably, the strong influence of high-risk HLA-DR alleles was abrogated after inclusion of EBV serology results.
  
  
  CONCLUSIONS
  The ability to discriminate MS cases and controls can be substantially enhanced by including anti-EBV serology as well as HLA-DR risk profiles. These findings support the relevance of EBV-specific immunity in MS pathogenesis, and implicate both HLA-dependent and HLA-independent immune responses against EBNA-1 as prominent disease risk factors.
authors.affiliation: Institute for Immunology & Infectious Diseases, Murdoch University, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Strautins
authors.forename: M
authors.initials: M
authors.lastname: Tschochner
authors.forename: I
authors.initials: I
authors.lastname: James
authors.forename: L
authors.initials: L
authors.lastname: Choo
authors.forename: D S
authors.initials: DS
authors.lastname: Dunn
authors.forename: M
authors.initials: M
authors.lastname: Pedrini
authors.forename: A
authors.initials: A
authors.lastname: Kermode
authors.forename: W
authors.initials: W
authors.lastname: Carroll
authors.forename: D
authors.initials: D
authors.lastname: Nolan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000914:Antibodies, Viral / Q000276:immunology*; D016022:Case-Control Studies; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D006684:HLA-DR Antigens
keywords: EBV; ELISA; HLA; Multiple sclerosis; genetics; immunology