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

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark trn{at}ssi.dk

K Rostgaard

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

J Askling

Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden

R Steffensen

Department of Clinical Immunology, Aalborg Hospital, Aalborg, Denmark

A Oturai

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark

C Jersild

Department of Clinical Immunology, Skejby Hospital, Aarhus, Denmark

N Koch-Henriksen

National Institute of Public Health, Copenhagen, Denmark; Department of Neurology, Aalborg Hospital, Aalborg, Denmark

PS Sørensen

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark

H Hjalgrim

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

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 DRB1*15 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 DRB1*15 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, DRB1*15 carried a 2.4-fold (95% confidence interval [CI], 2.0–3.0) increased MS risk. In contrast, among persons with IM history, DRB1*15 was associated with a 7.0-fold (95% CI, 3.3–15.4) increased MS risk. Thus, the MS risk conferred by HLA-DRB1*15 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 DRB1*15-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.

Key Words: epidemiology • HLA-DRB1*15 • immunology • infectious mononucleosis • multiple sclerosis

This version was published on April 1, 2009

Multiple Sclerosis, Vol. 15, No. 4, 431-436 (2009)
DOI: 10.1177/1352458508100037


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