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

• Published in: European journal of neurology Vol. 17; no. 11; pp. 1386 - 1389
• Main Authors: Ingram, G., Bugert, J. J., Loveless, S., Robertson, N. P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2010; John Wiley & Sons, Inc
• Subjects: Adult; Aged; Antibodies, Viral - blood; Antibodies, Viral - immunology; Biomarkers - metabolism; Disability Evaluation; Disease Progression; Enzyme-Linked Immunosorbent Assay - methods; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens - immunology; Female; Humans; Immunoglobulin G - blood; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - classification; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; prognosis; viral infections
• ISSN: 1351-5101; 1468-1331
• 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.