Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Mult Scler. 2011 Oct;17(10):1185-93. doi: 10.1177/1352458511408991. Epub 2011 Jun 17.
Elevated Epstein-Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized.
The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS.
We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks.
MS risk increased with increasing titers of anti-EBNA complex (p < 10(-9)) and anti-EBNA-1 (p = 5.8 × 10(-9)) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6-136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6-23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1.
Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.
EB 病毒（EBV）抗体滴度升高是多发性硬化症（MS）的危险因素，但这种关联的强度和一致性尚未得到很好的描述。
本研究旨在确定这种关联是否受到维生素 D 的混杂，是否受到性别或种族的修饰，以及 EBV 核抗原（EBNA）抗体作为 MS 标志物的有用性。
我们在美国军事人员中进行了一项前瞻性研究。在 222 名发生 MS 的个体和 444 名年龄、性别和种族/民族匹配的对照的血清样本中测量了针对 EBV 抗原的抗体滴度。使用条件逻辑回归估计相对风险。
MS 风险随抗-EBNA 复合物（p<10(-9)) 和抗-EBNA-1（p=5.8×10(-9)) 抗体滴度的增加而增加。抗-EBNA 复合物 IgG 滴度≥320 的个体与滴度<20 的个体相比，MS 风险高 36 倍（95%置信区间[CI] 9.6-136），抗-EBNA-1≥320 的个体与抗-EBNA-1<20 的个体相比，MS 风险高 8 倍（95%CI 2.6-23）。这些关联在性别和种族/民族群体中是一致的，并且与 25-羟维生素 D 水平无关。EBNA 复合物和 EBNA-1 的接收者操作特征（ROC）曲线下面积分别为 0.67 和 0.65。
发病前抗-EBNA 抗体的血清滴度是 MS 风险的强有力、可靠标志物，可用于 MS 风险评分。
