Mounting evidence proves that multiple sclerosis (MS) is a disease of autoimmune nature, but no known biomarker is strongly correlated with the clinical course (Leibovitch et al., 2018). Several genetic and environmental factors are considered to increase the risk of MS. Epstein–Barr virus (EBV) has been identified as an infectious agent in the pathogenesis of MS (Kvistad et al., 2014; Thacker et al., 2006; Hohlfeld and Wekerle, 2004; Bjornevik et al., 2022; Zdimerova et al., 2021), , , . This belief is further strengthened by the fact that having a history of infectious mononucleosis increases the risk of MS by 2.3 times and seronegative individuals have a lower risk profile (Thacker et al., 2006). EBV infection is more prevalent in childhood and adolescence, which could explain the higher risk of MS in these populations than in those infected later (Tracy et al., 2012; Lang et al., 2002; Handel et al., 2010; Ascherio and Munger, 2007), , , , , . After the primary infection, EBV stays dormant in B and epithelial cells for the rest of life, asymptomatic for the most part (Lassmann et al., 2011). These infected B memory cells are thought to be responsible for activating autoreactive T-cells (Greenfield and Hauser, 2018). Viral peptides of EBV can act as a stimulator by molecular mimicry mechanisms (Sospedra and Martin, 2005). Pathology studies found B-cells infected with EBV in the meningeal ectopic lymphoid deposits, which are recently thought to play a significant role in the pathogenesis of cortical lesions, though not all studies can identify infected meningeal B-cells (Veroni et al., 2018). Early cortical lesion load and rate of atrophy are among the main determinants of future disability, and EBV is thought to propagate meningeal inflammation (Magliozzi et al., 2010; Crawford et al., 2006).

Most studies investigated the correlation of antibody titer with the treatment outcome (Wandinger et al., 2000; Ascherio and Munger, 2007). Considering EBV infection is related to the early MS development and inflammatory activity in the brain, we aimed to investigate the burden of EBV antibody titer on attack severity and lesion load at the early stages of MS diagnosis.