Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk

K. Strautins, M. Tschochner, I. James, L. Choo, D. S. Dunn, M. Pedrini, A. Kermode, W. Carroll, D. Nolan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Risk factors for multiple sclerosis (MS) include human leukocyte antigen (HLA)-DR and Epstein-Barr virus (EBV)-specific antibody responses, including an epitope within EBV nuclear antigen 1 (EBNA-1) that is of recent interest. Objective: The objective of this paper is to assess case-control associations between MS risk and anti-EBV antibody levels as well as HLA-DR profiles, gender and age in a population-based cohort. Methods: Serological responses to EBV were measured in 426 MS patients and 186 healthy controls. HLA-DR typing was performed using sequence-based methods. Results: MS patients had significantly higher levels of antibodies against epitope-specific and polyspecific EBNA-1 and viral capsid antigen (VCA), compared with controls (all p < 10-15). In regression analyses, anti-EBNA-1 and anti-VCA antibody levels, protective HLA-DR 04/07/09 alleles and gender (all p <0.003) contributed independently to a model that classified cases and controls with an odds ratio < 20 (sensitivity 92%, specificity 64%). Notably, the strong influence of high-risk HLA-DR alleles was abrogated after inclusion of EBV serology results. Conclusions: The ability to discriminate MS cases and controls can be substantially enhanced by including anti-EBV serology as well as HLA-DR risk profiles. These findings support the relevance of EBV-specific immunity in MS pathogenesis, and implicate both HLA-dependent and HLA-independent immune responses against EBNA-1 as prominent disease risk factors.

Original languageEnglish
Pages (from-to)286-294
Number of pages9
JournalMultiple Sclerosis
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 2014

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