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

Manuel Comabella1,2, Harald Hegen3, Luisa M Villar4

  • 1Servei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Journal of Neurology
|December 12, 2024
PubMed
Abstract

Insights

Primary progressive multiple sclerosis (PPMS) patients show heightened immune responses to Epstein-Barr virus nuclear antigen 1 (EBNA1). Chronic cytomegalovirus (CMV) infection may also be linked to progressive MS.

Area of Science:

  • Neuroimmunology
  • Virology
  • Multiple Sclerosis Research

Background:

  • Viral infections' impact on multiple sclerosis (MS) susceptibility and progression is primarily studied in relapse-onset MS (RMS).
  • Limited research exists on immune responses to common viruses in primary progressive MS (PPMS).
  • Understanding these responses in PPMS is crucial for disease management and therapeutic strategies.

Purpose of the Study:

  • To investigate immune responses to ubiquitous viruses in patients with PPMS.
  • To compare viral antibody levels in PPMS patients with healthy controls.
  • To explore potential correlations between antiviral immunity and disease progression in PPMS.

Main Methods:

  • Antibody responses to Epstein-Barr virus (EBV) (EBNA1, VCA), human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were measured.
  • A cohort of 68 PPMS patients with an 8-year follow-up was compared to 66 age- and sex-matched healthy controls.
  • Seroprevalence rates and specific antibody titers were analyzed.

Main Results:

  • PPMS patients exhibited significantly increased humoral immune responses to the latent EBV-encoded nuclear antigen-1 (EBNA1) compared to controls.
  • No significant differences were found in responses to lytic EBV capsid antigen (VCA) or other tested viral antigens (HHV-6, measles).
  • Seroprevalence rates for human cytomegalovirus (HCMV) were notably higher in the PPMS cohort. Baseline antiviral immune responses did not correlate with disability progression.

Conclusions:

  • Elevated immune responses targeting EBNA1 are selectively increased in PPMS, suggesting a role in both RMS and PPMS pathogenesis.
  • Chronic HCMV infection is associated with progressive MS, warranting further investigation.
  • These findings highlight specific viral-associated immune dysregulation in progressive MS.