Current and past Epstein-Barr virus infection in risk of initial CNS demyelination
Lucas, RM and Ponsonby, AL and Dear, K and Valery, P and Pender, MP and Burrows, JM and Burrows, SR and Chapman, C and Coulthard, A and Dwyer, DE and Dwyer, T and Kilpatrick, T and Lay, MLJ and McMichael, AJ and Taylor, BV and van der Mei, IAF and Williams, D, Current and past Epstein-Barr virus infection in risk of initial CNS demyelination, Neurology, 77, (4) pp. 371-379. ISSN 0028-3878 (2011) [Refereed Article]
To assess risk of a first clinical diagnosis of central nervous system demyelination (FCD) in relation to measures of Epstein Barr virus (EBV) infection within the context of other known risk factors.
Multicentre incident case-control study. FCD cases (n=282) aged 18-59 years and controls (n=558, matched on age, sex and region) were recruited from four Australian centres between 1 Nov 2003 and 31 Dec 2006. A nested study (n=215 cases, n=216 controls) included measurement of whole blood quantitative EBV DNA load and serum EBV-specific antibodies. Conditional logistic regression was used to analyse case-control differences.
There were no significant case-control differences in the proportion with detectable EBV DNA (55.8% vs. 50.5% respectively, p=0.28), or in quantitative EBV DNA load (p=0.33). Consistent with previous work, higher anti-EBV-specific IgG titers and a history of infectious mononucleosis were associated with increased FCD risk and there was an additive interaction with HLA-DRB1*1501 status. We found additional interactions between high anti-EBNA IgG titer and SNPs in HLA-A [AOR=19.84 (95%CI 5.95-66.21) for both factors compared to neither] and CTLA-4 genes [AOR=0.31 (95%CI 0.13-0.76) for neither factor compared to both]. EBV DNA load was lower at higher serum 25-hydroxyvitamin D concentrations in controls (r=-0.17, p=0.01). An adverse effect of higher EBV DNA load on FCD risk was increased with higher 25-hydroxyvitamin D concentration [p(interaction)=0.02]
Past infection with EBV, but not current EBV DNA load in whole blood, is significantly associated with increased FCD risk. These associations appear to be modified by immune-related gene variants.