Han L, Zhang Y, Wang Q, Xin M, Yang K, Lei K, Sun M
1 Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
2 Shandong University Qilu Hospital (Qingdao Branch), Qingdao, Shandong, China.
Lupus. 2018 Jan 1:961203317753069. doi: 10.1177/0961203317753069.
Epstein-Barr (EB) virus infection has long been speculated to evoke systemic lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN) system activation, we aimed to discover the relationship between the two in the progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with IFNα in patient sera were detected with enzyme-linked immunosorbent assays. The EB virus DNA load was detected by real-time quantitative polymerase chain reaction. Peripheral blood mononuclear cells both from patients and controls were isolated immediately. The mRNA from these samples was subjected to real-time PCR for the latent genes EBNA1, EBNA2 and LMP1 of EB virus, as well as four IFN-stimulated genes (ISGs) ( OASL, MX1, ISG15 and LY6E). The antibody results were used to determine the stage of EBV infection (lytic, latent, or previous). Results SLE patients had a higher rate of lytic infection defined as positive EBV-VCA IgM antibody (39.66% vs 10.53%, p = 0.027), but not the EB virus DNA load. Patients with lytic EB virus infection had higher SLEDAI scores than patients with non-lytic infection (15.24 ± 2.63 vs 13.79 ± 3.24, p = 0.012). LMP1 was the only EBV gene that had a higher expression level in SLE patients than in healthy controls (3.26 ± 2.95 vs 1.00 ± 2.89, p = 0.000). It was also positively correlated with SLEDAI scores ( r = 0.462, p = 0.000). Levels of IFNα and the four ISGs were all significantly higher in SLE patients than in healthy controls ( p < 0.05). LMP1 was positively correlated with the four ISGs ( r = 0.403 ∼ 0.494, p < 0.05) in SLE patients but not in healthy controls ( r = -0.153 ∼ 0.129, p > 0.05). Neither EBNA1 nor EBNA2 was correlated with the ISGs in SLE patients or in healthy controls. Conclusions The SLE patients had higher rates of lytic EB virus infection and higher latent gene LMP1 expression, which might be associated with the development and/or the progression of SLE via the type I IFN pathway. The underlying mechanism needs more study.
长期以来，人们一直推测爱泼斯坦 - 巴尔（EB）病毒感染会引发系统性红斑狼疮（SLE）。由于病毒感染可诱导干扰素（IFN）系统激活，我们旨在在中国住院患者队列中探究两者在SLE病程中的关系。方法 从116例SLE患者和76例健康对照中分离外周血单个核细胞和血清。采用酶联免疫吸附测定法检测患者血清中抗EBV - VCA（IgM和IgG）、抗EBNA（IgG）抗体以及IFNα。通过实时定量聚合酶链反应检测EB病毒DNA载量。立即分离患者和对照的外周血单个核细胞。对这些样本的mRNA进行实时PCR，检测EB病毒的潜伏基因EBNA1、EBNA2和LMP1，以及四个干扰素刺激基因（ISG）（OASL、MX1、ISG15和LY6E）。抗体检测结果用于确定EBV感染阶段（裂解期、潜伏期或既往感染）。结果 以EBV - VCA IgM抗体阳性定义的SLE患者裂解感染率较高（39.66%对10.53%，p = 0.027），但EB病毒DNA载量无差异。裂解期EB病毒感染患者的SLEDAI评分高于非裂解感染患者（15.24±2.63对13.79±3.24，p = 0.012）。LMP1是唯一在SLE患者中表达水平高于健康对照的EBV基因（3.26±2.95对1.00±2.89，p = 0.000）。它也与SLEDAI评分呈正相关（r = 0.462，p = 0.000）。SLE患者的IFNα水平和四个ISG水平均显著高于健康对照（p < 0.05）。在SLE患者中，LMP1与四个ISG呈正相关（r = 0.403～0.494，p < 0.05），而在健康对照中无相关性（r = -0.153～0.129，p > 0.05）。在SLE患者或健康对照中，EBNA1和EBNA2均与ISG无相关性。结论 SLE患者具有较高的裂解期EB病毒感染率和较高的潜伏基因LMP1表达，这可能通过I型干扰素途径与SLE的发生和/或进展相关。潜在机制需要更多研究。
