Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis.

BACKGROUND

Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus infection presenting as infectious mononucleosis (IM) are recognized as risk factors for multiple sclerosis (MS). However, their combined effect and possible interaction on MS risk is not known.

OBJECTIVE

To assess the association between HLA-DRB1*15 and risk of MS in persons with and without IM.

METHODS

We compared the prevalence of DRB115 in MS patients with (n = 76) and without (n = 1,836) IM with the corresponding distributions in blood donors with (n = 62) and without (n = 484) IM histories. This allowed us to estimate the relative risk of MS associated with DRB115 in the presence and absence, respectively, of previous IM. We then estimated the interaction between DRB1*15 and IM as the ratio of the two individual odds ratios.

RESULTS

In IM-naïve individuals, DRB115 carried a 2.4-fold (95% confidence interval [CI], 2.0-3.0) increased MS risk. In contrast, among persons with IM history, DRB115 was associated with a 7.0-fold (95% CI, 3.3-15.4) increased MS risk. Thus, the MS risk conferred by HLA-DRB115 was 2.9 (95% CI, 1.3-6.5)-fold stronger in the presence than in the absence of IM. Combined with previous results, this result indicates that DRB115-positive persons with a history of IM may be at a 10.0-fold (95% CI, 6.0-17.9) increased risk of MS compared with persons who are DRB1*15 and IM-naïve.

CONCLUSION

DRB1*15 and IM may act in synergy causing MS.