EBV and MS: is EBV the cause?

Yet another meta-analysis on EBV and MS. Is EBV the cause of MS? #MSBlog #MSResearch

Almohmeed et al. Systematic Review and Meta-Analysis of the Sero-Epidemiological Association between Epstein Barr Virus and Multiple Sclerosis. PLoS One. 2013 Apr 9;8(4):e61110. doi: 10.1371/journal.pone.0061110. Print 2013.

BACKGROUND: A role for Epstein Barr virus (EBV) in MS has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MSers compared to controls, but many studies have since been published, and there is a need to apply more rigorous systematic review methods.

METHODOLOGY & PRINCIPAL FINDINGS: They examined the link between EBV and MS by conducting a systematic review and meta-analysis of case-control and cohort studies that examined the prevalence of anti-EBV antibodies in the serum of cases and controls. They searched Medline and Embase databases from 1960 to 2012, with no language restriction. The odds ratios (OR) for anti-EBV antibodies sero-positivity were calculated, and meta-analysis conducted. Quality assessment was performed. 39 studies were included. Quality assessment found most studies reported acceptable selection and comparability of cases and controls. However the majority had poor reporting of ascertainment of exposure. Most studies found a higher sero-prevalence of anti-EBNA IgG and anti-VCA IgG in cases compared to controls. The results for anti-EA IgG were mixed with only half the studies finding a higher sero-prevalence in cases. The meta-analysis showed a significant OR for sero-positivity to anti-EBNA IgG and anti-VCA IgG in MS cases (4.5 [95% confidence interval (CI) 3.3 to 6.6, p<0.00001] and 4.5 [95% CI 2.8 to 7.2, p<0.00001] respectively). However, funnel plot examination suggested publication bias for the reporting of the anti-EBNA IgG. No significant difference in the OR for sero-positivity to anti-EA IgG was found (1.4 [95% CI 0.9 to 2.1, p = 0.09]).

CONCLUSION & SIGNIFICANCE: These findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of laboratory analyses.

“These findings are in keeping with our recent meta-analysis. It seems that many groups are repeating similar work. Thankfully the results are consistent. EBV infection and an antibody response to certain EBV proteins or antigens, in particular EBNA-1 (EBV nuclear antigen-1) is strongly associated with MS. Is this association causal? I think it is. How do you prove it? You target EBV with specific anti-viral drugs and see what happens to MS. This hypothesis is the core hypothesis that underpins The Charcot Project.”

“The following video from our 4th MS Research Day is an update on the Charcot Project.”

Other posts of interest:

Multiple Sclerosis Research: Medical student gets top marks for MS 

15 Jul 2012
Medical student gets top marks for MS study. Julia Pakpoor has just finished her third year studying medicine at Brasenose College, Oxford. As part of her intercalated year Julia did a project on MS that was supervised by Ram 
01 Jul 2012
Research: EBV is the cause of MS. Epub: Pakpoor et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler. 2012 Jun 11. BACKGROUND: Epstein-Barr virus 
08 Sep 2012
Pakpoor et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler. 2012 Jun 11. It is also apparent that you have to be infected with EBV before you develop 

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.


  • "Target EBV with anti-viral drugs….." . Unfortunately there are no effective anti-virals to EBV. Acyclovir, ganciclovir, valacyclovir family and foscarnet used in other herpes viruses are ineffective. I thought Charcot project was looking at HERVs as trigger?

    • yes there are. Anti-CD20 and anti-CD19 are good anti-EBV drugs In addition, raltegravir is also active against herpes viruses. In addition, we have another drug that we think is effective as well. More on that later.

  • Epstein Barr infects and immortalises B cells in the immune system. It could be these cells rather than the free virus itself that are the cause. What happens to MS in people treated for Hodgkin's Lymphoma? Anyone know? Mixed cellularity Hodgkins normally contains Epstein Barr.

    • Rituxan eliminates B cells, and has proven to be quite effective in treating RRMS. Not so much for the progressive forms of the disease, although the PPMS trials did seem to hint at a subset of patients for which the drug impeded progression…

  • Rituxan is an Anti-CD20 drug and targets all B cells that show CD20 so when Gavin said they were anti-EBV they are actually anti-CD20 including infected cells.

    I was wondering more about the effect on those treated with ABVD or Stanford V chemotherapy treatments and if they had an effect. They do not clear the body completely of infection so I would not a long term effect, but for a short time the virus is likely to be more active because the immune system is suppressed but most of the long term infected B cells have been killed. So may indicate which is important.

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