Cytomegalovirus seropositivity is negatively associated with multiple sclerosis

Background: Epidemiological data suggest a role for common viruses in the pathogenesis of multiple sclerosis (MS), and recent data showed a negative association of past cytomegalovirus (CMV) infection on pediatric MS risk. Objective: Our aim was to analyze the association of CMV infection with MS risk in an adult case-control material. A meta-analysis was performed to validate our findings. Methods: Epidemiological Investigation in MS (EIMS) is a case-control study with incident cases and population-based controls. Anti-CMV antibody titers were measured with ELISA, and HLA-A and DRB1 genotyping was performed with SSP-PCR, in 658 MS cases, who all fulfilled the McDonald criteria for MS, and 786 controls. Results: CMV seropositivity was associated with a decreased MS risk, OR = 0.73 (0.58-0.92 95% CI), p = 0.005, adjusted for index age, gender, smoking, sun exposure, EBNA1 IgG titer and HLA-A*02 and DRB1*15. When we removed all cases and controls younger than 18 years at index, the protective effect was still apparent. Conclusions: CMV is negatively associated with adult-onset MS pathology, consistent with results from a study on pediatric MS cases. It remains to be shown whether this negative association is due to a true protective effect of CMV infection on MS risk.