Department of Clinical Laboratories, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PLoS One. 2018 Mar 1;13(3):e0193171. doi: 10.1371/journal.pone.0193171. eCollection 2018.
Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) which is prevalent in South China, and its association with systemic lupus erythematosus (SLE) or other autoimmune diseases has not been studied in the mainland of China. The EBV serological tests have been performed on patients with various diseases or manifestations for years at our institution and their values need to be evaluated.
For routine medical purposes, anti-EB viral capsid antigen (VCA) IgG, IgA and IgM antibodies, anti-EBV diffuse early antigen (EA-D) IgA antibodies, and anti-EBV nuclear antigen-1(EBNA-1) IgG antibodies were tested with commercial enzyme-linked immunosorbent assay (ELISA) in patients visiting Peking Union Medical College Hospital between 2013 and 2017. The test results were analyzed in this retrospective study.
There were a total of 11122 serum samples available to be tested in the study. As indicators of past EBV infection, the prevalence of VCA-IgG/EBNA1-IgG were 66.6%/58.5%, 84.3%/78.8%, 92.9%/87.0% and 98.5%/95.4% in patients aged under 5 years, 6-10 years, 11-20 years and 21-30 years old, respectively, and these values maintained at this highest rate as age increased further. The prevalence of VCA-IgM, as a parameter of acute EBV infection, was 14.6%, 10.2%, 10.4%, 6.3% and 3.1% in patients aged under 5 years, 6-10 years,11-20 years, 21-30 years, 31-40 years old, respectively, and decreased to 2%~3% in older patients. Patients with elevated serum liver enzymes were more likely to have a higher prevalence of EA/D IgA antibody (P < 0.01) and young patients (≤30 years) with lymphadenopathy were more likely to have higher prevalence of VCA-IgM antibody (P < 0.01). The prevalence of VCA-IgA and EAD-IgA were 87.0% and 59.2% in NPC patients, respectively, and both were significantly higher (P < 0.001) than that in non-NPC patients. The prevalence of VCA-IgA was 45.4% and 25.6% in SLE patients and patients with other autoimmune diseases, respectively, which were significantly (P < 0.001) and mildly (P = 0.039) higher than their controls. In pediatric SLE patients between 6 and10 years old, the prevalence of VCA-IgG, VCA-IgA and EBNA1-IgG was 100%, 59.5% and 100%, respectively, all being significantly higher than the age (6-10y) related controls (P< 0.01). In the 705 cerebral spinal fluid (CSF) specimens, VCA-IgG, VCA-IgM, VCA-IgA and EAD-IgA were found to be positive in 12.1%, 0.15%, 0.25% and 0.25%, respectively. There were 157 paired specimens (CSF and serum were collected simultaneously) and VCA-IgG was identified as positive in 12.7% of the CSF and 100% of the serum specimens.
Around 98% of Chinese patients were infected with EBV before 30 years of age and the highest rate of acute EBV infection were observed in patients under 5 years old. EBV infection was found to be associated with elevated serum liver enzymes, NPC and SLE. Acute anti-EBV antibody was valued for young patients with lymphadenopathy but limited value for CNS neuropathy.
EB 病毒（EBV）与鼻咽癌（NPC）有关，而 NPC 在华南地区很常见，其与系统性红斑狼疮（SLE）或其他自身免疫性疾病的关系尚未在内地进行研究。我们机构多年来一直对各种疾病或表现的患者进行 EBV 血清学检测，需要对其检测值进行评估。
为了常规医疗目的，采用商业酶联免疫吸附试验（ELISA）检测了 2013 年至 2017 年间来我院就诊的患者的抗 EBV 衣壳抗原（VCA）IgG、IgA 和 IgM 抗体、抗 EBV 弥散早期抗原（EA-D）IgA 抗体和抗 EBV 核抗原-1（EBNA-1）IgG 抗体。本研究回顾性分析了这些检测结果。
共有 11122 份血清样本可供检测。作为 EBV 既往感染的指标，VCA-IgG/EBNA1-IgG 的流行率分别为 5 岁以下、6-10 岁、11-20 岁和 21-30 岁患者的 66.6%/58.5%、84.3%/78.8%、92.9%/87.0%和 98.5%/95.4%，且随着年龄的进一步增加，这些值保持在最高水平。VCA-IgM 作为急性 EBV 感染的参数，5 岁以下、6-10 岁、11-20 岁、21-30 岁和 31-40 岁患者的流行率分别为 14.6%、10.2%、10.4%、6.3%和 3.1%，且在老年患者中降至 2%~3%。血清肝酶升高的患者更可能出现 EA/D IgA 抗体阳性（P<0.01），且年轻（≤30 岁）伴淋巴结病的患者更可能出现 VCA-IgM 抗体阳性（P<0.01）。NPC 患者的 VCA-IgA 和 EAD-IgA 流行率分别为 87.0%和 59.2%，均显著高于非 NPC 患者（P<0.001）。SLE 患者和其他自身免疫性疾病患者的 VCA-IgA 流行率分别为 45.4%和 25.6%，均显著高于各自的对照组（P<0.001）和轻度高于对照组（P=0.039）。6-10 岁的儿科 SLE 患者中，VCA-IgG、VCA-IgA 和 EBNA1-IgG 的流行率分别为 100%、59.5%和 100%，均显著高于相应年龄组（6-10 岁）的对照组（P<0.01）。在 705 份脑脊液（CSF）标本中，VCA-IgG、VCA-IgM、VCA-IgA 和 EAD-IgA 的阳性率分别为 12.1%、0.15%、0.25%和 0.25%。有 157 份配对标本（CSF 和血清同时采集），VCA-IgG 在 CSF 标本中的阳性率为 12.7%，在血清标本中的阳性率为 100%。
约 98%的中国患者在 30 岁之前感染 EBV，且 5 岁以下患者的急性 EBV 感染率最高。EBV 感染与血清肝酶升高、NPC 和 SLE 有关。急性抗 EBV 抗体对伴有淋巴结病的年轻患者有价值，但对中枢神经系统神经病变的价值有限。
