Low sun exposure acts synergistically with high Epstein−Barr nuclear antigen 1 (EBNA-1) antibody levels in multiple sclerosis etiology

Abstract

Background: Among multiple sclerosis (MS) patients, an association has been observed between low levels of vitamin D and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels. However, whether sun exposure/vitamin D moderates the role of Epstein-Barr virus (EBV) infection in MS etiology is unclear. We aimed to investigate potential synergistic effects between low sun exposure and elevated EBNA-1 antibody levels regarding MS risk. Methods: We used a population-based case−control study involving 2017 incident cases of MS and 2443 matched controls. We used logistic regression models to calculate the odds ratios of MS with 95% confidence intervals (CIs) in subjects with different sun exposure habits and EBNA-1 status. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Results: Low sun exposure acted synergistically with high EBNA-1 antibody levels (AP 0.2, 95% CI 0.03–0.3) in its association to increased MS risk. The interaction was present regardless of HLA-DRB1*15:01 status. Conclusions: Low sun exposure may either directly, or indirectly by affecting vitamin D levels, synergistically reinforce pathogenic mechanisms, such as aspects of the adaptive immune response, related to MS risk conveyed by EBV infection.