Investigation of the role of pregnancy and exposure to biological children in the onset of central nervous system demyelination

Background: Previous work has shown high levels of anti-Epstein Barr Virus (EBV) antibodies in individuals with multiple sclerosis (MS).Objectives: To examine history of glandular fever, anti-EBV antibody profile and whole blood viral load at first clinical diagnosis of central nervous system demyelination (FCD), compared to community controls. Methods: The Australian Multicentre Study of Environment and Immune Function (Ausimmune Study) recruited FCD cases and unaffected controls matched on age (18–59 years), sex and study region, between 1 November 2003 and 31 December 2006. Data included history of glandular fever (yes/no), serum IgG antibody titres for EBNA complex, viral capsid antigen (VCA) and early antigen (EA), and whole blood quantitative EBV DNA viral load (measured using real-time polymerase chain reaction [PCR], primers and probe derived from BamH1 of the EBV genome and Namalwa cell line with 2 EBV copies per cell for the standard curve) expressed as EBV copies per ug of DNA. Conditional logistic regression was used to analyse case-control differences. Results: Past history of glandular fever (n=277 cases, n=538 controls) was associated with increased odds of being a FCD case (OR=1.87, 95% confidence interval [CI] 1.30–2.67). In a subsample (n=204 cases, n=210 controls), higher titres (log2) of anti-EBNA (OR=1.26, 95% CI 1.13–1.40), anti-VCA (OR=1.16, 95% CI 1.03– .32) and anti-EA-restricted (OR=1.16, 95% CI 1.04–1.29) but not anti-EAdiffuse (OR=1.06, 95% CI 0.93–1.21) antibodies, were associated with increased risk of being a FCD case. EBV load (n=215 cases, n=216 controls) was more likely to be positive in FCD cases than controls (56.3% vs. 49.5%), and was significantly correlated with anti-EBNA (p=0.02), anti-VCA (p<0.001) and anti-EA-restricted (p=0.001), but not anti-EAdiffuse (p=0.16) antibodies. Multivariate analyses are underway. Conclusions: History of glandular fever, or evidence of prior infection with EBV is associated with increased odds of being a FCD case, strengthening evidence that EBV infection is a risk factor for MS onset.