Antibodies to Epstein-Barr virus and myelin oligodendrocyte glycoprotein in childhood inflammatory demyelinating diseases of the central nervous system

Background: Epstein-Barr virus (EBV) has repeatedly been discussed to play a role in the pathogenesis of multiple sclerosis in both adults and children. Crossreactivity between viral proteins and CNS autoantigens has been proposed as a likely mechanism how autoimmune responses emerge following infection. The objective of this study was to investigate the prevalence of antibodies to EBV proteins in children presenting with a first episode of inflammatory demyelinating diseases of the central nervous system (CNS) and correlate those with the antibody response to native myelin oligodendrocyte protein (nMOG), a putative autoantigen involved in demyelinating diseases of the CNS.

Methods: Sera of children with acute disseminated encephalomyelitis (ADEM, n=19, mean age 5.2yrs) and clinically isolated syndrome (CIS, n=25, 9.2yrs) were obtained during the first clinical manifestation of a demyelinating disorder and compared with neurological (n=28, 6yrs) and healthy (n=30, 11yrs) controls. We detected and quantified IgG and IgM antibodies against the extracellular part of nMOG by flow cytometry using a cell line transfected with human MOG. EBV-specific antibody responses to EBV Nuclear Antigen-1 (EBNA-1) and Early Antigen (EA) were assessed by ELISA.

Results: We found significantly higher titer of IgG antibodies to nMOG in children with both ADEM and CIS compared with healthy or neurological controls (p<0.0001), whereas only three patients, all of them presenting with ADEM, had elevated anti-nMOG IgM titers. Anti-EBNA-1 IgG antibody titers were significantly elevated in CIS patients compared with controls. 45% of controls, 42% of ADEM and 64% of CIS patients showed an elevated IgG response to EBNA-1, whereas IgM antibodies to EA were only detected in three children, all of them affected by ADEM. We did not observe any correlation between anti-EBNA-1 and anti-nMOG IgG antibody titers. However, two patients with elevated anti-nMOG IgM also showed an IgM response to EA.

Conclusion: Recent EBV infection might be associated with the development of anti-nMOG IgM antibodies in ADEM as two of three children with anti-nMOG IgM also showed IgM reactivity to EA. In contrast, the development of CIS may be associated with latent EBV infection, as suggested by the higher prevalence of EBNA-1 antibodies in children affected by CIS. The lack of correlation between IgG antibody responses to nMOG and EBV proteins does not suggest that antibody responses to nMOG are triggered by EBV.