Kreft Karim L, Van Nierop Gijsbert P, Scherbeijn Sandra M J, Janssen Malou, Verjans Georges M G M, Hintzen Rogier Q
Department of Neurology (K.L.K., G.P.V.N., M.J., R.Q.H.), MS Center ErasMS (K.L.K., M.J., R.Q.H.), Department of Viroscience (G.P.V.N., S.M.J.S., G.M.G.M.V.), and Department of Immunology (M.J., R.Q.H.), Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Neurol Neuroimmunol Neuroinflamm. 2017 Oct 12;4(6):e406. doi: 10.1212/NXI.0000000000000406. eCollection 2017 Nov.
To assess whether MS genetic risk polymorphisms (single nucleotide polymorphism [SNP]) contribute to the enhanced humoral immune response against Epstein-Barr virus (EBV) infection in patients with MS.
Serum anti-EBV nuclear antigen 1 (EBNA-1) and early antigen D (EA-D) immunoglobulin γ (IgG) levels were quantitatively determined in 668 genotyped patients with MS and 147 healthy controls. Anti-varicella-zoster virus (VZV) IgG levels were used as a highly prevalent, non-MS-associated control herpesvirus. Associations between virus-specific IgG levels and MS risk SNPs were analyzed.
IgG levels of EBNA-1, but not EA-D and VZV, were increased in patients with MS compared with healthy controls. Increased EBNA-1 IgG levels were significantly associated with risk alleles of SNP rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11), and rs7200786 (CLEC16A/CIITA) in an interaction model and a trend toward significance for rs3135388 (HLA-DRB1*1501). In addition, risk alleles of rs694739 (PRDX5/BAD) and rs11581062 (VCAM1) were independently associated and interacted with normal EBNA-1 IgG levels. None of these interactions were associated with EA-D and VZV IgG titers.
Several MS-associated SNPs significantly correlated with differential IgG levels directed to a latent, but not a lytic EBV protein. The data suggest that the aforementioned immune-related genes orchestrate the aberrant EBNA-1 IgG levels.
评估多发性硬化症（MS）遗传风险多态性（单核苷酸多态性[SNP]）是否有助于增强MS患者针对爱泼斯坦-巴尔病毒（EBV）感染的体液免疫反应。
对668例已进行基因分型的MS患者和147名健康对照者的血清抗EBV核抗原1（EBNA-1）和早期抗原D（EA-D）免疫球蛋白γ（IgG）水平进行定量测定。抗水痘-带状疱疹病毒（VZV）IgG水平用作高度流行的、与MS无关的对照疱疹病毒。分析病毒特异性IgG水平与MS风险SNP之间的关联。
与健康对照相比，MS患者中EBNA-1的IgG水平升高，而EA-D和VZV的IgG水平未升高。在一个相互作用模型中，EBNA-1 IgG水平升高与SNP rs2744148（SOX8）、rs11154801（MYB）、rs1843938（CARD11）和rs7200786（CLEC16A/CIITA）的风险等位基因显著相关，并且rs3135388（HLA-DRB1*1501）有显著意义的趋势。此外，rs694739（PRDX5/BAD）和rs11581062（VCAM1）的风险等位基因与正常EBNA-1 IgG水平独立相关并相互作用。这些相互作用均与EA-D和VZV IgG滴度无关。
几个与MS相关的SNP与针对潜伏性而非裂解性EBV蛋白的不同IgG水平显著相关。数据表明，上述免疫相关基因协调了异常的EBNA-1 IgG水平。
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