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

Published

Journal Article

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.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.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).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.

Full Text

Cited Authors

  • Lucas, RM; Ponsonby, A-L; Dear, K; Valery, P; Pender, MP; Burrows, JM; Burrows, SR; Chapman, C; Coulthard, A; Dwyer, DE; Dwyer, T; Kilpatrick, T; Lay, M-LJ; McMichael, AJ; Taylor, BV; van der Mei, IAF; Williams, D

Published Date

  • July 13, 2011

Published In

Volume / Issue

  • 77 / 4

Start / End Page

  • 371 - 379

PubMed ID

  • 21753179

Pubmed Central ID

  • 21753179

Electronic International Standard Serial Number (EISSN)

  • 1526-632X

International Standard Serial Number (ISSN)

  • 0028-3878

Digital Object Identifier (DOI)

  • 10.1212/wnl.0b013e318227062a

Language

  • eng