Epstein-Barr Virus Serologic Profiles in Multiple Sclerosis and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Although the link between Epstein-Barr virus (EBV) and multiple sclerosis (MS) is well established, geographic variation in EBV epidemiology warrants region-specific data from Asian populations. Beyond MS, the role of EBV in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains far less studied. This study aimed to compare EBV serostatus and antibody titers in patients with MS, MOGAD, and controls in a Korean cohort.

We analyzed MS (n = 130), MOGAD (n = 125), and untreated tumor controls without known EBV association (n = 132). MS and controls were frequency-matched to MOGAD by age at sampling. Serum Epstein-Barr nuclear antigen 1 (EBNA1) IgG, viral capsid antigen (VCA) IgG, VCA IgM, and early antigen (EA) IgG were measured using chemiluminescence immunoassays (LIAISON, DiaSorin). EBV seropositivity was defined as EBNA1 IgG or VCA IgG positivity, and serologic findings suggestive of possible recent infection/reactivation were defined as positivity for VCA IgM or EA IgG.

EBV seropositivity was nearly universal in MS, MOGAD, and controls (98.5%, 98.4%, and 99.2%, p = 0.751). EBNA1 responses differed across groups, with the frequency of EBNA1 IgG levels exceeding the upper reportable limit (>600 U/mL) being highest in MS, compared with MOGAD and controls (66.2% vs 33.6% vs 43.9%; p < 0.001). In three-group analyses using controls as reference, MS had higher EBNA1 IgG levels (adjusted geometric mean ratio [aGMR], 1.54; p = 0.006), whereas MOGAD did not. For VCA IgG, MS did not differ from controls, whereas MOGAD showed lower levels than controls (aGMR, 0.72; p = 0.018). Among patients with MS and MOGAD, models additionally adjusted for disease-related factors indicated that EBNA1 IgG and VCA IgG levels were higher in MS (aGMR, 1.97; p < 0.001 and aGMR, 1.42; p = 0.018, respectively), while ongoing treatment at sampling was associated with lower VCA IgG levels (aGMR, 0.64; p = 0.007). Serologic findings suggestive of possible recent EBV infection or reactivation were comparable across groups.

In this Korean cohort, MS showed stronger EBNA1 responses than MOGAD and controls, extending prior evidence on the relevance of EBNA1 in MS to an Asian population. The absence of a similar pattern in MOGAD suggests that the contribution of EBV may differ between the 2 diseases.