Current and past Epstein-Barr virus infection in risk of initial CNS demyelination

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. and Williams, D. (2011) Current and past Epstein-Barr virus infection in risk of initial CNS demyelination. Neurology, 77 4: 371-379. doi:10.1212/WNL.0b013e318227062a

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Author 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.
Title Current and past Epstein-Barr virus infection in risk of initial CNS demyelination
Journal name Neurology   Check publisher's open access policy
ISSN 0028-3878
Publication date 2011-07-26
Sub-type Article (original research)
DOI 10.1212/WNL.0b013e318227062a
Volume 77
Issue 4
Start page 371
End page 379
Total pages 9
Place of publication Philadelphia, PA, U.S.A.
Publisher Lippincott Williams & Wilkins
Collection year 2012
Language eng
Formatted 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.
Keyword Systemic-lupus-erythematosus
Real-time PCR
Sun exposure
Viral load
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 42 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 03 Aug 2011, 12:42:02 EST by Matthew Lamb on behalf of School of Medicine