BACKGROUND: The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with MS risk. Interaction between these two factors has been proposed.
OBJECTIVES: The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.
METHODS: Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MSers and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed.
RESULTS: The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402-502, and domain EBNA-1385-420; p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found.
CONCLUSIONS: This study confirms that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.