Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
Hannes Vietzen, Laura M. Kühner, S. Berger, Markus Ponleitner, Marianne Graninger, Charlotte Pistorius, Christof Jungbauer, Markus Reindl, Henrieke Saucke, Franziska Kauth, Eva‐Maria Wendel, Kevin Rostásy, Markus Breu, Barbara Kornek, Gabriel Bsteh, Thomas Berger, Paulus Rommer, Elisabeth Puchhammer-Stöckl
Abstract
Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1381-452 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1381-452-specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1381-452-specific antibody titers from 324 relapsing-remitting MS patients and 324 matched controls in longitudinal follow-up plasma samples, starting from the individual’s EBV-seroconversion. In MS patients, significantly elevated EBNA-1381-452-specific IgG titers are identified that are increased already as early as nine months after EBV-seroconversion (OR:5.7; 95% CI: 4.1-8.1; P < 0.0001) and a median 5.4 years prior to MS diagnosis. Especially, the presence of continuously high EBNA-1381-452-specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion (P < 0.0001). Thus, the quantification of EBNA-1381-452-specific IgG antibody levels may provide a prognostic biomarker to determine the individual’s risk for the diagnosis of MS. Multiple sclerosis (MS) is linked to immune responses triggered by Epstein-Barr virus (EBV). Here, the authors demonstrate that elevated EBNA-1-specific IgG antibody titers, detectable soon after EBV seroconversion, are associated with individual MS risk potentially serving as a prognostic biomarker.