Lack of replication of interaction between EBNA1 IgG and smoking in risk for multiple sclerosis.

BACKGROUND

Epstein-Barr virus infection, smoking, HLA-A02, and DRB115 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-DRB115, and A02, 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, DRB115, or absence of A02, although in a conditional analysis the interaction with absence of A02 becomes significant. However, we observed interactions on the additive scale between EBNA1 IgG and DRB115 (AP = 0.34, 95% confidence interval 0.11-0.57, p = 5 × 10⁻³) and between EBNA1 IgG and absence of A02 (AP = 0.36, 0.13-0.59, p = 2 × 10⁻³) but not between smoking and DRB115 and EBNA1 IgG. The interaction between EBNA1 IgG and DRB1*15 was not significant in the conditional analysis.

CONCLUSION

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.