Epstein-Barr virus antibodies in serum and DNA load in saliva are not associated with radiological or clinical disease activity in patients with early multiple sclerosis

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.

Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

“…This study represents the largest EBV-CIS population evaluated to date. In a different study, including CIS, RRMS, and PMS, all had evidence of EBV serology and confirmed diagnosis of MS. Further support comes from a recent study by Gieß et al [90] reporting association of EBV infection with early-onset MS. EBV serology correlated with early diagnostic conversion from CIS to MS. However, neither 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.…”

Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

“…Regarding EBV, the association of this virus and relapses in MS is unclear 11,12 . However, EBV has been postulated as a primary cause of neurodegeneration in MS due to the presence of EBV infected B cells in CNS and the external immune reaction driven by EBV replication or by EBV-infected B cells presenting CNS antigens 13 .…”

CD70 Deficiency Associated With Chronic Epstein-Barr Virus Infection, Recurrent Airway Infections and Severe Gingivitis in a 24-Year-Old Woman

“…Real time PCR was used for the detection of CMV DNA targets the US17 gene, and for EBV the BNRF1 p143 gene, respectively, as previously described (13,14). The nucleic acid was extracted from EDTA plasma (CMV) or from EDTA whole blood (EBV).…”