Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis
Manuel Comabella, Harald Hegen, Luisa María Villar, Konrad Rejdak, Augusto Sao‐Avilés, Malina Behrens, Jaume Sastre‐Garriga, Neus Mongay‐Ochoa, Klaus Berek, Sergio Martínez‐Yélamos, Francisco Pérez‐Miralles, Ahmed Abdelhak, Franziska Bachhuber, Hayrettin Tumani, Jan Lycke, Pere Carbonell‐Mirabent, Adrián Valls Carbó, Igal Rosenstein, Roberto Álvarez‐Lafuente, Tamara Castillo‐Triviño, David Otaegui, Sara Llufriú, Yolanda Blanco, Antonio Sánchez, Antonio García‐Merino, Nicolás Fissolo, Lucía Gutiérrez, Javier Villacieros‐Álvarez, Enric Monreal, Heinz Wiendl, Xavier Montalbán, Jan D. Lünemann
Abstract
BACKGROUND AND OBJECTIVES: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS). METHODS: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age. RESULTS: Compared with controls, PPMS patients showed increased humoral immune responses to the EBV-encoded nuclear antigen-1 (EBNA1), but not to the lytic EBV capsid antigen (VCA) or to other viral antigens. Seroprevalence rates for HCMV were significantly higher in PPMS. Antiviral immune responses at baseline did not correlate with disability progression over time. DISCUSSION: Elevated immune responses toward EBNA1 are selectively increased in people with primary progressive disease, indicating a link between EBNA1-targeting immune responses and the development of both RMS and PPMS. Our data also suggest that chronic HCMV infection is associated with progressive MS.