Nielsen T R, Rostgaard K, Askling J, Steffensen R, Oturai A, Jersild C, Koch-Henriksen N, Sørensen P S, Hjalgrim H
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Mult Scler. 2009 Apr;15(4):431-6. doi: 10.1177/1352458508100037. Epub 2009 Jan 19.
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.
To assess the association between HLA-DRB1*15 and risk of MS in persons with and without IM.
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.
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.
DRB1*15 and IM may act in synergy causing MS.
人类白细胞抗原（HLA）-DRB1*15以及表现为传染性单核细胞增多症（IM）的爱泼斯坦-巴尔病毒感染均被视为多发性硬化症（MS）的风险因素。然而，它们对MS风险的联合作用及可能的相互作用尚不清楚。
评估HLA-DRB1*15与有或无IM者患MS风险之间的关联。
我们比较了有IM（n = 76）和无IM（n = 1836）的MS患者中DRB115的患病率，以及有IM病史（n = 62）和无IM病史（n = 484）的献血者中的相应分布情况。这使我们能够分别估计既往有和无IM时与DRB115相关的MS相对风险。然后我们将DRB1*15与IM之间的相互作用估计为两个个体优势比的比值。
在无IM史的个体中，DRB115使MS风险增加2.4倍（95%置信区间[CI]，2.0 - 3.0）。相比之下，在有IM病史的人群中，DRB115与MS风险增加7.0倍（95%CI，3.3 - 15.4）相关。因此，HLA-DRB115在有IM时赋予的MS风险比无IM时强2.9倍（95%CI，1.3 - 6.5）。结合既往结果，该结果表明有IM病史的DRB115阳性者患MS的风险可能比DRB1*15阴性且无IM史者高10.0倍（95%CI，6.0 - 17.9）。
DRB1*15和IM可能协同作用导致MS。
