Latham L B, Lee M J, Lincoln J A, Ji N, Forsthuber T G, Lindsey J W
Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA.
Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
Acta Neurol Scand. 2016 Jan;133(1):17-24. doi: 10.1111/ane.12417. Epub 2015 May 4.
The objective of this study was to determine whether reactivation of Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with MS disease activity on MR imaging.
Subjects with early, active relapsing-remitting MS were studied for 16 weeks with blood and saliva samples collected every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood mononuclear cells from each blood sample and tested the immune response to EBV, autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the proliferative response and the number of interferon-γ secreting cells with ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva with quantitative PCR. On MRI, we measured number and volume of contrast enhancing and T2 lesions. We tested for correlation between the immunologic assays and the MRI results, assessing different time intervals between the MRI and immunologic assays.
We studied 20 subjects. Ten had enhancing lesions on one or more MRI scans and one had new T2 lesions without enhancement. The most significant correlation was between proliferation to autologous LCL and the number of combined unique active lesions on MRI 4 weeks later. Both proliferation and number of cells secreting interferon-γ in response to LCL correlated with the number of enhancing lesions 8 weeks later.
We find evidence for correlation of antiviral immune responses in the blood with subsequent disease activity on MRI scans.
本研究的目的是确定爱泼斯坦-巴尔病毒（EBV）的重新激活或抗EBV免疫反应的激活是否与磁共振成像（MR）上的多发性硬化症（MS）疾病活动相关。
对早期活动性复发缓解型MS患者进行了16周的研究，每2周采集血液和唾液样本，每4周进行脑部MRI检查。我们从每个血液样本中分离出外周血单个核细胞，并检测其对EBV、自体EBV感染的淋巴母细胞系（LCL）、人类疱疹病毒6型（HHV6）、水痘带状疱疹病毒（VZV）、破伤风和丝裂原的免疫反应。我们用酶联免疫斑点法（ELISPOT）测量增殖反应和分泌干扰素-γ的细胞数量。我们用定量聚合酶链反应（PCR）测量血液和唾液中EBV、HHV6和VZV DNA的含量。在MRI上，我们测量了对比增强和T2病变的数量和体积。我们测试了免疫测定与MRI结果之间的相关性，评估了MRI和免疫测定之间的不同时间间隔。
我们研究了20名受试者。10人在一次或多次MRI扫描中有增强病变，1人有新的无增强的T2病变。最显著的相关性是自体LCL增殖与4周后MRI上合并的独特活动性病变数量之间的相关性。对LCL的增殖反应和分泌干扰素-γ的细胞数量均与8周后增强病变的数量相关。
我们发现血液中的抗病毒免疫反应与随后MRI扫描上的疾病活动相关的证据。
