18th Meeting of the European Neurological Society
07.06.2008 - 11.06.2008
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Home - 09.06.2008 - Multiple sclerosis 2

Multiple sclerosis 2

Monday, June 09, 2008, 16:00 - 16:15

Investigation of role of peripheral EBV reactivation in driving multiple sclerosis disease activity as measured by gadolinium enhanced MRI

R. Farrell, D. Antony, D. Clark, J. Swanton, L. Fisniku, Z. Khaleeli, A.J. Thompson, D.H. Miller, G. Giovannoni (London, GB)

Objective: To measure Epstein Barr virus activity and serological responses in peripheral blood of subjects with Multiple Sclerosis and correlate this with new gadolinium-enhancing lesions on MRI.
Background: Multiple sclerosis is thought to be triggered in susceptible individuals by an environmental agent/infection. A substantial body of evidence links EBV with MS. Epidemiological studies have shown elevated levels of anti-EBV antibodies predate development of MS. Peripheral EBV reactivation has been linked to disease activity and recently EBV infected B cells have been described in postmortem brain tissue of subjects with MS.
Design/methods: 100 subjects involved in serial imaging studies were identified - 50 CIS, 25 RRMS, 25 PPMS. Subjects had serial Gd-enhanced MRIs over a 5-year period, at which time blood was stored. EBV DNA in blood was quantified by real-time qPCR and EBV serology for anti-EBNA1 IgG, anti-VCA IgG and anti-EBV IgM using commercial kits. Serology for other common viruses was also performed. Statistical analysis was performed using Anova, t-test and logistic regression models.
Results: All subjects had evidence of past EBV infection. EBV DNA was found in 5 subjects, IgM response to EBV was detected in 13 subjects all associated with Gd-enhancing lesions (ns). Significant differences in level of antibodies to EBNA1 and ratio of anti-EBNA1:VCA IgG antibodies were found between subgroups, highest in RRMS group compared with PPMS and CIS . EBNA1:VCA ratio (R=0.36, p<0.001) and EBNA1 (R=0.33, p<0.001) correlated with development of new Gd-enhancing lesions.
Conclusions/relevance: Subjects with active disease have elevated levels of EBNA-1 IgG specifically which may reflect the severity of the initial antigenic challenge (primary infection/infectious mononucleosis). No acute peripheral reactivation was found to be associated with new Gd lesions. This suggests the primary EBV infection has a role in triggering the disease. In other EBV related disorders specific antibody patterns have been described as risk factors for subsequent disease. Whether these antibodies have a pathogenic role or reflect the underlying immune dysregulation in MS remains unclear and requires further investigation.