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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]

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Copyright 2011 AAN Enterprises, Inc.

DOI: doi:10.1212/WNL.0b013e318227062a


Objectives 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. Methods 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. Results 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] Conclusion 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.

Item Details

Item Type:Refereed Article
Research Division:Health Sciences
Research Group:Epidemiology
Research Field:Epidemiology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Taylor, BV (Professor Bruce Taylor)
UTAS Author:van der Mei, IAF (Professor Ingrid van der Mei)
ID Code:71081
Year Published:2011
Web of Science® Times Cited:55
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-07-07
Last Modified:2012-04-26

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