Complete Epstein-Barr virus seropositivity in a cohort of pediatric onset multiple sclerosis: a comparison to other autoimmune diseases

Introduction: The role of Epstein-Barr virus (EBV) in multiple sclerosis (MS) pathogenesis is supported by the increased MS risk after infectious mononucleosis. This study aimed to evaluate EBV infection in our pediatric-onset MS (POMS) cohort. Methods: MS patients with disease onset < 18 years of age seen at Bambino Gesù Children's Hospital were included. We searched for anti-EBV nuclear antigen (EBNA) Immunoglobulin G (IgG) and anti-viral capsid antigen (VCA) IgG and IgM. For comparison, we analyzed the EBV infection seroprevalence in an age- and sex-matched control cohorts of immunologically-healthy children and subjects with non-neurological autoimmune diseases. Results: Fifty-seven POMS were included; all had a previous EBV infection. The controls' cohort included one-hundred and sixty-two patients with a median age of 12 years (range 6-17), encompassing two subgroups: non-autoimmune (i.e. primary headaches) and autoimmune controls, namely inflammatory bowel disease and juvenile idiopathic arthritis. In the control group, ninety-six (59%) were EBV seropositive. EBV seropositivity was significantly higher in POMS than in the controls' cohort (OR = 79.2, 95% C.I. 4.8-1305), and compared to autoimmune and non-autoimmune controls separately (p < 0.0001). Discussion: In our POMS cohort, EBV seropositivity was 100%, higher than previously reported. Our results support a disease-specific role of EBV in the MS development compared to other pediatric autoimmune disorders, consistent with evidence reported in adult-onset MS.