title: Lack of replication of interaction between EBNA1 IgG and smoking in risk for multiple sclerosis.
abstract: BACKGROUND
  Epstein-Barr virus infection, smoking, HLA-A*02, and DRB1*15 have all been proposed as risk factors for multiple sclerosis (MS). In 2010, Simon et al. described an interaction on the multiplicative scale between EBNA1 immunoglobulin G (IgG) and smoking regarding risk of MS, a finding that we attempted to replicate.
  
  
  METHODS
  This Swedish case-control study consisted of patients with newly diagnosed MS and matched controls. Using logistic regression, we analyzed association to MS risk and interactions between EBNA1 IgG and smoking, HLA-DRB1*15, and A*02, respectively, on the multiplicative scale. In addition, we analyzed interactions on the additive scale using attributable proportion due to interaction (AP).
  
  
  RESULTS
  We did not observe any interaction on the multiplicative scale between EBNA1 IgG and any of the 3 risk factors, smoking, DRB1*15, or absence of A*02, although in a conditional analysis the interaction with absence of A*02 becomes significant. However, we observed interactions on the additive scale between EBNA1 IgG and DRB1*15 (AP = 0.34, 95% confidence interval 0.11-0.57, p = 5 × 10⁻³) and between EBNA1 IgG and absence of A*02 (AP = 0.36, 0.13-0.59, p = 2 × 10⁻³) but not between smoking and DRB1*15 and EBNA1 IgG. The interaction between EBNA1 IgG and DRB1*15 was not significant in the conditional analysis.
  
  
  CONCLUSIONS
  We did not observe any interaction between EBNA1 IgG and smoking, regardless of scale used, and thus did not replicate the observations from Simon et al.
authors.affiliation: From the Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden. Emilie.Sundqvist@ki.se
authors.forename: Emilie
authors.initials: E
authors.lastname: Sundqvist
authors.forename: Peter
authors.initials: P
authors.lastname: Sundström
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lindén
authors.forename: Anna Karin
authors.initials: AK
authors.lastname: Hedström
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000378:metabolism*; D016022:Case-Control Studies; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology*; D012306:Risk; D012907:Smoking / Q000276:immunology* / Q000378:metabolism; D013548:Sweden; D014779:Virus Replication / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; C417029:EBV-encoded nuclear antigen 1