Don C. Gnocchi Foundation IRCCS - ONLUS, Piazzale Morandi 3, 20121, Milan, Italy.
Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
J Transl Med. 2018 Mar 27;16(1):80. doi: 10.1186/s12967-018-1450-6.
The etiopathology of multiple sclerosis (MS) is believed to include genetic and environmental factors. Human leukocyte antigen (HLA) alleles, in particular, are associated with disease susceptibility, whereas Epstein Barr Virus (EBV) infection has long been suspected to play a role in disease pathogenesis. The aim of the present study is to evaluate correlations between HLA alleles and EBV infection in MS.
HLA alleles, EBV viral load (VL) and serum anti-EBV antibody titers were evaluated in EBV-seropositive MS patients (N = 117) and age- and sex-matched healthy controls (HC; N = 89).
Significantly higher DNA viral loads (p = 0.048) and EBNA-1 antibody titer (p = 0.0004) were seen in MS compared to HC. EBV VL was higher in HLA-B07+ (p = 0.02) and HLA-DRB115+ (p = 0.02) MS patients, whereas it was lower in HLA-A02+ (p = 0.04) subjects. EBV VL was highest in HLA-A02-/B07+/DRB115+ patients and lowest in HLA-AA02+/B07-/DRB115- individuals (p < 0.0001). HLA-B07 resulted the most associated allele to EBV VL after multiple regression analysis considering altogether the three alleles, (p = 0.0001). No differences were observed in anti-EBV antibody titers in relationship with HLA distribution.
Host HLA-B*07 allele influence EBV VL in MS. As HLA-class I molecules present antigens to T lymphocytes and initiate immune response against viruses, these results could support a role for EBV in MS.
多发性硬化症（MS）的发病机制被认为包括遗传和环境因素。人类白细胞抗原（HLA）等位基因，特别是，与疾病易感性相关，而 Epstein Barr 病毒（EBV）感染长期以来一直被怀疑在疾病发病机制中起作用。本研究旨在评估 MS 中 HLA 等位基因与 EBV 感染之间的相关性。
评估 EBV 血清阳性 MS 患者（N=117）和年龄及性别匹配的健康对照者（HC；N=89）中的 HLA 等位基因、EBV 病毒载量（VL）和血清抗 EBV 抗体滴度。
与 HC 相比，MS 患者的 DNA 病毒载量（p=0.048）和 EBNA-1 抗体滴度（p=0.0004）显著更高。在 HLA-B07+（p=0.02）和 HLA-DRB115+（p=0.02）MS 患者中，EBV VL 更高，而在 HLA-A02+（p=0.04）患者中则更低。在 HLA-A02-/B07+/DRB115+患者中 EBV VL 最高，在 HLA-AA02+/B07-/DRB115-个体中最低（p<0.0001）。在考虑到这三个等位基因的多回归分析后，HLA-B07 是与 EBV VL 最相关的等位基因（p=0.0001）。在与 HLA 分布的关系中，未观察到抗 EBV 抗体滴度的差异。
宿主 HLA-B*07 等位基因影响 MS 中的 EBV VL。由于 HLA-I 类分子将抗原呈递给 T 淋巴细胞并启动针对病毒的免疫反应，这些结果可能支持 EBV 在 MS 中的作用。
