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Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risks
Journal article   Peer reviewed

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

K. Strautins, M. Tschochner, I. James, L. Choo, D. Dunn, M. Pedrini, A. Kermode, W. Carroll and D. Nolan
Multiple Sclerosis Journal, Vol.20(3), pp.286-294
2014
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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.

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Collaboration types
Domestic collaboration
Citation topics
1 Clinical & Life Sciences
1.203 Neuromuscular Disorders
1.203.147 Multiple Sclerosis
Web Of Science research areas
Clinical Neurology
Neurosciences
ESI research areas
Neuroscience & Behavior
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