Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis


  • S. Abrahamyan
  • B. Eberspächer
  • M.M. Hoshi
  • L. Aly
  • F. Luessi
  • S. Groppa
  • L. Klotz
  • S.G. Meuth
  • C. Schroeder
  • T. Grüter
  • B. Tackenberg
  • F. Paul
  • F. Then-Bergh
  • T. Kümpfel
  • F. Weber
  • M. Stangel
  • A. Bayas
  • B. Wildemann
  • C. Heesen
  • U. Zettl
  • C. Warnke
  • G. Antony
  • N. Hessler
  • H. Wiendl
  • S. Bittner
  • B. Hemmer
  • R. Gold
  • A. Salmen
  • K. Ruprecht


  • Journal of Neurology Neurosurgery and Psychiatry


  • J Neurol Neurosurg Psychiatry 91 (7): 681-686


  • OBJECTIVE: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. RESULTS: EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. CONCLUSION: The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.