Abstract
ObjectiveTo investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS).MethodsEBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls. EBV DNA load was measured in saliva of 48 patients and 50 controls. Patients underwent clinical assessment with the Expanded Disability Status Scale (EDSS) and 3 Tesla magnetic resonance imaging at baseline and after a median of 20 months of follow-up (n = 63 for MRI, n = 71 for EDSS). The association of EBV parameters with occurrence of a second relapse, indicating conversion to clinically definite MS (CDMS), was evaluated over a median of 35 months of follow-up after the first clinical event (n = 89).ResultsEBNA-1 IgG antibody frequency (p = 0.00005) and EBNA-1 and VCA IgG antibody levels (p<0.0001 for both) were higher in patients than in controls. EBV DNA load in saliva did not differ between groups. Neither EBV antibody levels nor DNA load in saliva were associated with baseline or follow-up number or volume of T2-weighted (T2w) or contrast enhancing lesions, number of Barkhof criteria or the EDSS, or with the number of new T2w lesions, T2w lesion volume change or EDSS change on follow-up. Likewise, levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to CDMS.ConclusionsWhile these findings confirm the association of EBV infection with early MS, neither EBNA-1 nor VCA IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with CIS/early RRMS. These data are compatible with the concept that EBV may be a trigger for MS acting very early during the development of the disease.
Highlights
Infection with the Epstein-Barr virus (EBV) is a strong risk factor for multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system [1, 2]
Levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to clinically definite MS (CDMS). While these findings confirm the association of EBV infection with early MS, neither Epstein-Barr nuclear antigen-1 (EBNA-1) nor viral capsid antigen (VCA) IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS)
We investigated whether EBNA-1 and viral capsid antigen (VCA) IgG antibody levels in serum, as well as EBV DNA load in saliva, are associated with clinical and magnetic resonance imaging (MRI) markers of disease activity, severity and progression in a cohort of 100 patients with CIS or early relapsing-remitting MS (RRMS)
Summary
Infection with the Epstein-Barr virus (EBV) is a strong risk factor for multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system [1, 2]. EBV seroprevalence in patients with MS is practically universal, indicating that MS risk among EBV seronegatives is extremely low [1, 3,4,5]. Among healthy individuals infected with EBV, MS risk increases with increasing serum titers of antibodies to Epstein-Barr nuclear antigen-1 (EBNA-1) and the EBV nuclear antigen complex (EBNAc) [8,9,10,11,12]. Patients with MS or with a clinically isolated syndrome (CIS, i.e. a first clinical event suggestive of MS) have elevated levels of antibodies against EBV, in particular against EBNA-1 [13,14,15,16,17,18]
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