Background: It remains uncertain whether the presence of serum anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in healthy individuals contributes to predict their risk of developing multiple sclerosis (MS).

Methods: Prospective, nested case-control study of more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum Repository. A total of 126 MS cases and 252 controls matched by age, sex, race/ethnicity, and dates of blood collection were included in the analysis. An ELISA was used to detect IgM and IgG antibodies to MOG. Analyses were conducted with and without adjustment for serum titers of antibodies to the Epstein-Barr nuclear antigen (EBNA), which are an established risk factor for MS.

Results: The presence of anti-MOG IgG antibodies in serum was associated with an increase in risk of developing MS (relative risk for anti-MOG IgG+/IgM- vs seronegativity to both anti-MOG IgM and IgG: 2.03; 95% CI: 1.19–3.46; p = 0.01). This association, however, was attenuated and no longer significant after adjustment for titers of antibodies to EBNA, which were higher among individuals positive for anti-MOG antibodies.

Conclusion: Our findings suggest that although individuals with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have an increased risk of developing multiple sclerosis, this association may at least in part reflect cross-reactivity between MOG and Epstein-Barr nuclear antigen.