Higher EBV response is associated with more severe gray matter and lesion pathology in relapsing multiple sclerosis patients: A case-controlled magnetization transfer ratio study

Mult Scler. 2020 Mar;26(3):322-332. doi: 10.1177/1352458519828667. Epub 2019 Feb 13.


Background: Epstein-Barr virus (EBV) infection has been associated with higher clinical activity and risk of multiple sclerosis (MS).

Objective: To evaluate associations between EBV-specific humoral response and magnetization transfer ratio (MTR)-derived measure in MS patients and healthy controls (HCs).

Methods: The study included 101 MS patients (69 relapsing-remitting multiple sclerosis (RRMS) and 32 secondary-progressive multiple sclerosis (SPMS)) and 41 HCs who underwent clinical, serological, and magnetic resonance imaging (MRI) investigations. MTR values of T1 or T2 lesion volume (LV), normal-appearing (NA) brain tissue (NABT), gray matter (NAGM), and white matter (NAWM) were obtained. Enzyme-linked immunosorbent assay was used to quantify EBV antibody levels. Partial correlations corrected for MRI strength were used, and Benjamini-Hochberg-adjusted p-values < 0.05 were considered significant.

Results: MS patients had significantly higher anti-EBV nuclear antigen-1 (EBNA-1) titer when compared to HCs (107.9 U/mL vs 27.8 U/mL, p < 0.001). Within the MS group, higher serum anti-EBNA-1 titer was significantly correlated with lower T1-LV MTR (r = -0.287, p = 0.035). Within the RRMS group, higher serum anti-EBNA-1 titer was associated with T1-LV MTR (r = -0.524, p = 0.001) and NAGM MTR (r = -0.308, p = 0.043). These associations were not present in HCs or SPMS patients.

Conclusion: Greater EBV humoral response is associated with lower GM MTR changes and focal destructive lesion pathology in RRMS patients.

Keywords: EBNA-1; EBV; MTR; demyelination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / blood
  • Multiple Sclerosis, Chronic Progressive / diagnostic imaging
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • White Matter / diagnostic imaging
  • White Matter / pathology


  • Antibodies, Viral
  • Epstein-Barr Virus Nuclear Antigens
  • EBV-encoded nuclear antigen 1