Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis

Abstract

Epstein–Barr virus; Human cytomegalovirus; Multiple sclerosis

Virus de Epstein-Barr; Citomegalovirus humano; Esclerosis múltiple

Virus d'Epstein-Barr; Citomegalovirus humà; Esclerosi múltiple

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.

Open Access funding enabled and organized by Projekt DEAL. The authors thank Kerstin Stein (University Hospital of Münster, Department of Neurology with Institute of Translational Neurology) for expert technical assistance. This project has received funding from the European Union’s Horizon Europe Research and Innovation Actions under grant no. 101137235 (BEHIND-MS).