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.
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 MSpatients and 186 healthy controls. HLA-DR typing was performed using sequence-based methods. RESULTS:MSpatients 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.
Authors: Yuan Zhou; Ming Chen; Steve Simpson; Robyn M Lucas; Jac C Charlesworth; Nicholas Blackburn; Ingrid van der Mei; Anne-Louise Ponsonby; Bruce V Taylor Journal: Neurol Sci Date: 2017-11-10 Impact factor: 3.307
Authors: Yuan Zhou; Steve Simpson; Jac C Charlesworth; Ingrid van der Mei; Robyn M Lucas; Anne-Louise Ponsonby; Bruce V Taylor Journal: Brain Behav Date: 2017-03-09 Impact factor: 2.708
Authors: María Inmaculada Domínguez-Mozo; Lorena López-Lozano; Silvia Pérez-Pérez; Ángel García-Martínez; María José Torrejón; Rafael Arroyo; Roberto Álvarez-Lafuente Journal: Front Immunol Date: 2022-09-14 Impact factor: 8.786
Authors: Monika Tschochner; Shay Leary; Don Cooper; Kaija Strautins; Abha Chopra; Hayley Clark; Linda Choo; David Dunn; Ian James; William M Carroll; Allan G Kermode; David Nolan Journal: PLoS One Date: 2016-02-05 Impact factor: 3.240