系统性红斑狼疮患者中 Epstein-Barr 病毒和人类疱疹病毒 6 感染。
Epstein‒Barr virus and human herpesvirus 6 infection in patients with systemic lupus erythematosus.
机构信息
The Department of Rheumatology and Immunology, The First Hospital of China Medical University, Shenyang, 110001, China.
Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, 19 Jiangsu Road, Qingdao, 266003, China.
出版信息
Virol J. 2023 Feb 12;20(1):29. doi: 10.1186/s12985-023-01987-3.
BACKGROUND
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the etiology is still unclear. Some studies have indicated that viral infection might contribute to the development of SLE.
METHODS
A total of 105 individuals with SLE and 110 matched healthy controls were tested for EBV-specific DNA fragments in peripheral blood monocytes by PCR-Southern blotting. The expression of EBV-encoded genes was determined by RT-PCR and Southern blotting in EBV-positive patients. Serum EBV-specific IgM antibody was determined by ELISA. HHV-6 DNA in peripheral blood monocytes of those SLE patients and normal controls was tested by nested PCR.
RESULTS
Statistical analysis showed that the EBV-positive rate of SLE patients was significantly higher than that of the control group (χ = 87.329, P = 0), while the difference in the HHV-6-positive rate between the two groups was not significant (P > 0.05). An association of EBV and HHV-6 positivity in SLE patients was found (P = 0, r = 0.38). The EBV IgM level was significantly higher in SLE patients than in healthy controls (χ = 25.184, P = 0). Forty-two of the 75 EBV DNA-positive specimens were positive for EBNA2 mRNA, and an association between EBV EBNA2 mRNA and anti-Sm antibody positivity was found (P = 0, r = 0.409). LMP1 mRNA was positive in 2 SLE patients with active phase, and no LMP2A mRNA expression was detected in EBV DNA-positive specimens. EBV early gene BARF1 mRNA was detected in 2 cases of EBV-positive SLE patients, and these 2 patients were also HHV-6 DNA positive. Thirty-eight patients were BcLF1 mRNA positive, and 33 of them were HHV-6 positive as well. These factors were associated (χ = 15.734, P = 0). The expression of the EBV immediate early gene BZLF1 was negative in all 75 EBV-positive SLE patients.
CONCLUSIONS
The results suggest that EBV infection might be related to the occurrence of SLE. Although there is no direct evidence that HHV-6 infection is associated with the development of SLE, EBV and HHV-6 infection may have a coacceleration effect in SLE patients. This study provides a new theoretical and experimental basis for the study of viral etiology and the prevention and treatment of SLE.
背景
系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，其病因仍不清楚。一些研究表明，病毒感染可能导致 SLE 的发生。
方法
采用 PCR-印迹杂交法检测 105 例 SLE 患者和 110 例匹配的健康对照者外周血单个核细胞中 EBV 特异性 DNA 片段。通过 RT-PCR 和印迹杂交法检测 EBV 阳性患者中 EBV 编码基因的表达。采用 ELISA 法检测血清 EBV 特异性 IgM 抗体。采用巢式 PCR 法检测 SLE 患者和正常对照者外周血单个核细胞中的 HHV-6 DNA。
结果
统计学分析显示，SLE 患者 EBV 阳性率明显高于对照组（χ²=87.329，P=0），而两组 HHV-6 阳性率差异无统计学意义（P>0.05）。SLE 患者 EBV 和 HHV-6 阳性存在相关性（P=0，r=0.38）。SLE 患者 EBV IgM 水平明显高于健康对照组（χ²=25.184，P=0）。75 例 EBV DNA 阳性标本中 42 例检测到 EBNA2 mRNA，且 EBV EBNA2 mRNA 与抗 Sm 抗体阳性存在相关性（P=0，r=0.409）。2 例活动期 SLE 患者 LMP1 mRNA 阳性，EBV DNA 阳性标本中未检测到 LMP2A mRNA 表达。2 例 EBV 阳性 SLE 患者检测到 EBV 早期基因 BARF1 mRNA，且这 2 例患者均为 HHV-6 DNA 阳性。38 例患者 BcLF1 mRNA 阳性，其中 33 例同时为 HHV-6 阳性。这些因素存在相关性（χ²=15.734，P=0）。75 例 EBV 阳性 SLE 患者的 EBV 早期即刻基因 BZLF1 表达均为阴性。
结论
本研究提示 EBV 感染可能与 SLE 的发生有关。虽然尚无直接证据表明 HHV-6 感染与 SLE 的发生有关，但 EBV 和 HHV-6 感染可能在 SLE 患者中具有协同加速作用。本研究为病毒病因学研究及 SLE 的防治提供了新的理论和实验依据。
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