EBV antibodies and MRI activity

Could interferon-beta be working via suppressing lytic EBV infection? #MSBlog #MSResearch

“The study below supports our previous publication that antibody levels to EBV nuclear antigen 1 (EBNA-1) correlates with disease activity on MRI. The higher the antibody level the more likely you were to have MRI activity as detected using MRI. As always is this association or causation? Is EBV driving disease activity or is disease activity resulting in higher levels of antibodies the EBV protein EBNA-1? I wish I could answer that question, but I can’t. What is interesting is that EBNA-1 is the protein that is responsible for keeping the EBV genome in the latent or dormant phase and is large expressed in B cells. Could it be that raised levels are a marker of EBV-infected B-cell expansion? What does this mean for the EBV hypothesis? It suggests that latent EBV-infected B cells may be playing a role in MS and that targeting these cells may be a good therapeutic strategy. Can we do this? Yes, we can and this is what most of the highly effective DMTs do already; they target B cells amongst other cells. The one class of treatment that specifically targets B cells are the B cell depleting anti-CD20 monoclonoal antibodies, that have been discussed in detail on this blog. This data also reassures me to continue to focus on EBV as a possible cause of MS.”

“An interesting observation from this study is that IgM antibodies to the viral capsid antigen (VCA) predicted a treatment response to IFNbeta. This will need to be confirmed. IgM antibodies are usually produced as part of the initial immune response and disappear after a few months. VCA is a protein that is expressed as part of active EBV infection; i.e. when the virus is in its so called lytic phase. Lytic or cell lysis simple refers to the bursting open of the cell to release active viral particles. Does this suggest that MSers who have active lytic EBV infection are more likely to respond to interferon-beta? This would be worth exploring further in larger data sets.”
From the Newfoundland and Labrador Public Health Laboratory

Epub: Kvistad et al. Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis. Mult Scler. 2014 May 19. pii: 1352458514533843.

BACKGROUND: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and MS disease activity, but the results have been conflicting.

OBJECTIVES:  The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response.

METHODS: A total of 87 MSers were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model.

RESULTS: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most MSers were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment.

CONCLUSIONS: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


    • I guess you disagree them ProfG

      Multiple sclerosis therapy and Epstein–Barr virus antibody titres
      Anti-Epstein–Barr virus (EBV) nuclear antigen-1 (anti-EBNA-1) IgG antibody titres have been found to correlate with MRI and clinical measures of disease activity in MS. Despite being a putative biomarker of disease activity, the effect of disease modifying drugs on anti-EBNA-1 IgG titre has not yet been determined.

      In this study, we investigated the effect of interferon-beta and natalizumab therapy on prospective sera anti-EBNA-1 IgG titres, using a quantitative ELISA, in patients with relapsing-remitting MS.

      For both the interferon-beta and natalizumab group, there was no significant difference between pre-therapy and post-therapy anti-EBNA-1 IgG titre. There was also no significant difference between the groups with regard to mean percentage change in anti-EBNA-1 IgG titre over 12 months of treatment.

      This study suggests that anti-EBNA-1 IgG titre is unlikely to be a good surrogate marker for disease activity in patients on disease modifying drugs.


      •Anti-EBNA-1 IgG titre is a putative biomarker in multiple sclerosis.
      •We measured titres pre and post-natalizumab and interferon beta.
      •Anti-EBNA-1 IgG titres do not change after disease modifying treatment.
      •This argues against the use of anti-EBNA-1 IgG as a biomarker.

By Prof G



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