Key result
Anti-EBV antibody levels combined with HLA-DR alleles and gender classified multiple sclerosis cases and controls with an odds ratio >20 (sensitivity 92%, specificity 64%).
Why the study?
Do anti-EBV antibody levels and HLA-DR profiles associate with multiple sclerosis risk?
Case-Control (n=612)
Do anti-EBV antibody levels and HLA-DR profiles associate with multiple sclerosis risk?
Odds Ratio: 20
p-value: p=< 0.003
Combining anti-EBV serology with HLA-DR risk profiles substantially enhances the ability to discriminate MS cases from controls.
May enhance MS risk discrimination via anti-EBV and HLA-DR; hypothesis-generating and requires prospective validation before clinical use.
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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Strautins et al. (2013) conducted a case-control in Multiple sclerosis (n=612). Anti-EBV antibody levels and HLA-DR profiles vs. Healthy controls was evaluated on Multiple sclerosis risk (case vs control classification) (OR > 20, p=< 0.003). Anti-EBV antibody levels combined with HLA-DR alleles and gender classified multiple sclerosis cases and controls with an odds ratio >20 (sensitivity 92%, specificity 64%).
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