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Title: Current and past Epstien-Barr virus infection in risk of initial CNS demyelination.
Authors: Lucas, R. M.
Ponsonby, A. L.
Dear, K.
Valery, P.
Pender, M. P.
Burrows, J. M.
Burrows, S. R.
Chapman, C.
Coulthard, A.
Dwyer, D. E.
Dwyer, T.
Kilpatrick, T.
Lay, M. L. J.
McMichael, A. J.
Taylor, B. V.
van der Mei, I. A. F.
Williams, D.
Issue Date: 2011
Publisher: American Acadamy of of Neurology
Place of publication: Philladelphia, PA
Publication Title: Neurology
Volume: 77
Issue: 4
Start Page: 371
End Page: 379
Abstract: OBJECTIVES: To assess risk of a first clinical diagnosis of CNS demyelination (FCD) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors. METHODS: This was a multicenter 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 4 Australian centers between November 1, 2003, and December 31, 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 analyze 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 immunoglobulin G (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 (adjusted odds ratios [AOR] = 19.84 [95% confidence interval (CI) 5.95 to 66.21] for both factors compared to neither) and CTLA-4 genes (AOR = 0.31 [95% CI 0.13 to 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. This study was undertaken with data obtained from Ballarat Health Services - B. Knight.
ISSN: 0028-3878
Internal ID Number: 00271
Type: Journal Article
Appears in Collections:Research Output

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