Farrell, R. A., Antony, D., Wall, G. R., Clark, D.A., Fisniku, L., Swanton, J., Khaleeli, Z., Schmierer, K., Miller, D. H. and Giovannoni, G. (2009) Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI. Neurology, 73(1), pp. 32-38. (doi: 10.1212/WNL.0b013e3181aa29fe) (PMID:19458321) (PMCID:PMC2848585)
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Abstract
Background: Evidence suggests that Epstein-Barr virus (EBV) plays a role in triggering or perpetuating disease activity in multiple sclerosis (MS). Methods: We investigated 100 subjects (50 clinically isolated syndrome [CIS], 25 relapsing-remitting [RR] MS, 25 primary progressive [PP] MS) for 1) evidence of EBV reactivation and 2) disease activity as indicated by serial gadolinium (Gd)-enhanced MRIs over a 5-year period. EBV DNA in blood was quantified by real-time quantitative PCR and EBV serology for anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG), anti-viral capsid antigen (VCA) IgG, and anti-EBV IgM. Data were analyzed using repeated measures analysis, analysis of variance, and logistic regression analysis. Results: All subjects had serologic evidence of previous EBV infection, but no lytic reactivation was detected. Significant differences in EBNA-1 IgG titers were found between subgroups, highest in the RRMS cohort compared with PPMS (p < 0.001) and CIS (p < 0.001). Gd-enhancing lesions on MRI correlated with EBNA-1 IgG (r = 0.33, p < 0.001) and EBNA-1:VCA IgG ratio (r = 0.36, p <0.001). EBNA-1 IgG also correlated with change in T2 lesion volume (r = 0.27, p = 0.044) and Expanded Disability Status Scale score (r = 0.3, p = 0.035). Conclusions: The correlation between elevated Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) and gadolinium-enhancing lesions suggests an association between Epstein-Barr virus (EBV) infection and multiple sclerosis (MS) disease activity. The heightened immune response to EBV in MS is specifically related to EBNA-1 IgG, a marker of the latent phase of the virus. The lack of association between acute viral reactivation in the peripheral blood and Gd+ lesions suggests a limited role of the former in driving disease activity.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Clark, Dr Duncan |
Authors: | Farrell, R. A., Antony, D., Wall, G. R., Clark, D.A., Fisniku, L., Swanton, J., Khaleeli, Z., Schmierer, K., Miller, D. H., and Giovannoni, G. |
College/School: | College of Medical Veterinary and Life Sciences > School of Life Sciences |
Journal Name: | Neurology |
Publisher: | American Academy of Neurology |
ISSN: | 0028-3878 |
ISSN (Online): | 1526-632X |
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