title: The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis.
abstract: 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. 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).
  
  
  CONCLUSIONS
  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.
authors: Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
authors: Julia
authors: J
authors: Pakpoor
authors: Giulio
authors: G
authors: Disanto
authors: Jennifer E
authors: JE
authors: Gerber
authors: Ruth
authors: R
authors: Dobson
authors: Ute C
authors: UC
authors: Meier
authors: Gavin
authors: G
authors: Giovannoni
authors: Sreeram V
authors: SV
authors: Ramagopalan
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000453:epidemiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000209:etiology; D016017:Odds Ratio; D012306:Risk