title: Anti-EBNA-1 IgG is not a reliable marker of multiple sclerosis clinical disease activity.
abstract: BACKGROUND
  Sero-epidemiological studies have demonstrated the association between multiple sclerosis (MS) and prior Epstein-Barr virus (EBV) infection. It has been hypothesized that intermittent peripheral EBV reactivation may drive continuing central inflammation. Recent investigation has shown significant differences in median serum levels of anti-EBV nuclear antigen-1 (EBNA-1) IgG between disease subgroups and positive correlation with disease activity reflected by number of Gd-enhancing lesions and T2 lesion volume. These important data have led to hopes that anti-EBNA-1 IgG may be useful as an easily accessible and effective biomarker of disease activity.
  
  
  METHODS
  We examined the applicability of these findings in routine clinical practice, assessing a well-characterized cohort of 100 subjects (25 primary progressive, 25 stable relapsing remitting, 25 active relapsing remitting seen in acute relapse and 25 controls) for serum anti-EBNA-1 IgG using both the Liaison quantitative chemiluminescent assay and Biotest ELISA.
  
  
  RESULTS
  We were unable to show a difference in quantitative analysis of serum anti-EBNA-1 IgG levels between disease subgroups and no correlation with phenotypic characteristics including age at onset (r = -0.17, P = 0.16), disease duration (r = 0.03, P = 0.78), EDSS (r = 0.03, P = 0.78) or MSSS (r = 0.02, P = 0.9). In addition, there was only moderate correlation between the two test methods used (intraclass correlation coefficient 0.67; 0.56-0.78) suggesting potential problems with test interpretation.
  
  
  CONCLUSIONS
  We have been unable to determine a clinical value for serum anti-EBNA-1 IgG levels in MS or to confirm reported association with disease course and clinical disease activity.
authors.affiliation: Department of Neurosciences and Psychological medicine, Cardiff University, Cardiff, CF14 4XW, UK.
authors.forename: G
authors.initials: G
authors.lastname: Ingram
authors.forename: J J
authors.initials: JJ
authors.lastname: Bugert
authors.forename: S
authors.initials: S
authors.lastname: Loveless
authors.forename: N P
authors.initials: NP
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D004185:Disability Evaluation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000145:classification / Q000175:diagnosis* / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; C417029:EBV-encoded nuclear antigen 1