Strong association with remote EBV infection in children with MS as opposed to other acquired demyelinating disorders

Background The link between multiple sclerosis (MS) and Epstein-Barr virus (EBV) is well established in adults but less clear in paediatric cases. In addition, the role of EBV and other viral infections in acquired demyelinating syndromes (ADS), including paediatric MS and myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), remains unknown. This study explores viral infections in children with MS, MOGAD and other ADS. Methods Serum samples from paediatric patients in a Dutch multicentre ADS cohort were tested for seroprevalence of EBV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) using immunoassays. Results 31 children with MS, 26 with MOGAD and 15 with other ADS were included. Nearly all had prior HHV-6 infection (MS 87%, MOGAD 88% and ADS 93%). All children with MS had prior EBV exposure, compared with 50% in MOGAD and 67% in other ADS (p=0.001). EBV nuclear antigen 1 (EBNA-1) and viral capsid antigen antibody levels were particularly high in the MS group. CMV seroprevalence was lower in MS (35%) than in MOGAD (58%, p=0.13), despite older age at onset (16.0 vs 10.5 years). In children with MS, no significant correlations were found between EBNA-1 levels and clinical measures like annualised relapse rate, Expanded Disability Status Scale or the presence of black holes on MRI at baseline. Conclusions All children with MS show evidence of remote EBV infection, unlike MOGAD and other ADS. EBNA-1 levels are notably high in children with MS. Remote CMV infection appears more common in MOGAD. There are no associations between serology and clinical parameters.