Grahn Anna, Studahl Marie, Nilsson Staffan, Thomsson Elisabeth, Bäckström Malin, Bergström Tomas
Department of Infectious Diseases, Sahlgrenska University Hospital, Östra, SE-416 85 Gothenburg, Sweden.
Clin Vaccine Immunol. 2011 Aug;18(8):1336-42. doi: 10.1128/CVI.05061-11. Epub 2011 Jun 22.
Herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) cause serious central nervous system (CNS) diseases that are diagnosed with PCR using samples of cerebrospinal fluid (CSF) and, during later stages of such infections, with assays of intrathecal IgG antibody production. However, serological diagnoses have been hampered by cross-reactions between HSV-1 and VZV IgG antibodies and are commonly reported in patients with herpes simplex encephalitis (HSE). In this study we have evaluated VZV glycoprotein E (gE) as a new antigen for serological diagnosis of VZV-induced CNS infections. Paired samples of CSF and serum from 29 patients with clinical diagnosis of VZV CNS infection (n = 15) or HSE (n = 14), all confirmed by PCR, were analyzed. VZV gE and whole VZV were compared as antigens in enzyme-linked immunosorbent assays (ELISAs) for serological assays in which the CSF/serum sample pairs were diluted to identical IgG concentrations. With the gE antigen, none of the HSE patients showed intrathecal IgG antibodies against VZV, compared to those shown by 11/14 patients using whole-VZV antigen (P < 0.001). In the patients with VZV infections, significantly higher CSF/serum optical density (OD) ratios were found in the VZV patients using the VZV gE antigen compared to those found using the whole-VZV antigen (P = 0.001). These results show that gE is a sensitive antigen for serological diagnosis of VZV infections in the CNS and that this antigen was devoid of cross-reactivity to HSV-1 IgG in patients with HSE. We therefore propose that VZV gE can be used for serological discrimination of CNS infections caused by VZV and HSV-1.
单纯疱疹病毒1型（HSV-1）和水痘-带状疱疹病毒（VZV）可引起严重的中枢神经系统（CNS）疾病，这些疾病可通过使用脑脊液（CSF）样本进行PCR诊断，并且在这些感染的后期，可通过鞘内IgG抗体产生的检测来诊断。然而，HSV-1和VZV IgG抗体之间的交叉反应阻碍了血清学诊断，并且在单纯疱疹性脑炎（HSE）患者中普遍存在交叉反应的报道。在本研究中，我们评估了VZV糖蛋白E（gE）作为VZV诱导的CNS感染血清学诊断的新抗原。分析了29例临床诊断为VZV CNS感染（n = 15）或HSE（n = 14）的患者的配对CSF和血清样本，所有病例均经PCR确诊。在酶联免疫吸附测定（ELISA）中，将VZV gE和完整VZV作为抗原进行血清学检测，其中将CSF/血清样本对稀释至相同的IgG浓度。使用gE抗原时，与使用完整VZV抗原的11/14例患者相比，没有HSE患者显示出针对VZV的鞘内IgG抗体（P < 0.001）。在VZV感染患者中，与使用完整VZV抗原相比，使用VZV gE抗原的VZV患者的CSF/血清光密度（OD）比值明显更高（P = 0.001）。这些结果表明，gE是CNS中VZV感染血清学诊断的敏感抗原，并且该抗原在HSE患者中与HSV-1 IgG没有交叉反应。因此，我们建议VZV gE可用于血清学鉴别由VZV和HSV-1引起的CNS感染。
