Anti-EBNA-1 IgG is not a reliable marker of multiple sclerosis clinical disease activity

Eur J Neurol. 2010 Nov;17(11):1386-9. doi: 10.1111/j.1468-1331.2010.03083.x.


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.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Biomarkers / metabolism
  • Disability Evaluation
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / classification
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / immunology*


  • Antibodies, Viral
  • Biomarkers
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin G
  • EBV-encoded nuclear antigen 1