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 (EBV) infection is widely considered to be a risk factor for multiple sclerosis (MS). A previous meta-analysis estimated an odds ratio (OR) for MS in individuals seronegative for EBV of 0.06.
"This meant that if you were found to be EBV negative your chances of getting MS were very close to being zero compared to somebody who is EBV positive; a 94% lower risk. This study is a timely update of this previous analysis."
Given the potential importance of this finding, we aimed to establish a more precise OR for adult and paediatric onset MS in EBV seronegative individuals.
METHODS: PubMed and EMBASE searches were undertaken to identify studies investigating the association between MS and EBV. Twenty-two adult and three paediatric studies were included. ORs were calculated using a fixed effects model. A sub-group analysis based on the method of EBV detection was performed.
RESULTS: The OR for developing adult MS in EBV seronegatives was 0.18 (95% confidence interval (CI) 0.13-0.26)) and for paediatric MS was 0.18 (95% CI 0.11-0.30). Sub-group analysis on EBV detection method showed that studies which used immunofluoresence generated an OR=0.07 (95% CI 0.03-0.16); for those that used enzyme-linked immunosorbent assay (ELISA) OR=0.33 (95% CI 0.22-0.50) and for studies which used ELISA and immunofluoresence OR=0.00 (95% CI 0-0.43).
CONCLUSION: The sensitivity and specificity of the assay used to measure EBV antibody titres have an influence on the association between MS and EBV. Looking at studies where two independent methods are used and therefore are likely to be the most robust, EBV appears to be present in 100% of MS patients. This has implications for future studies of EBV in MS. MS patients without EBV infection, if they truly exist, should be studied in more detail.
"This study tells us two things. (1) The assays we use to assess whether or not you have had EBV are not that sensitive. In other words being negative on one assay means you may still have had EBV infection in the past; a false negative test. When you are negative using two different assays you are more likely to be EBV negative, a true negative test. This is a very important observation and has major implications on how we interpret the EBV data. (2) If you are EBV negative on two different assays your risk of getting MS is zero compared to someone who is EBV positive. This observation indicates that EBV is likely to be the cause of MS or at least fall in the causal pathway. This is why we need to focus our research attention on EBV; how does EBV trigger and/or drive MS disease activity? Hence my frustration when our recent grant application was turned down to test an anti-EBV drug in MS. Don't worry we are not giving up; we are going to generate some more basic lab data and when we go back for funding the case will be water tight. We do need your help; if you get the chance please keep letting the World and MS stakeholders know how important the Charcot Project is."
CoI: This work is from Team G and was done as part of an MRC funded grant. I would also like to point out that Julia Pakpoor is a medical student. It is unusual for someone in medical school to publish such an important paper. Well done Julia!