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

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. [ABSTRACT FROM AUTHOR]