Centro de Investigaciones en Ciencias de La Vida, Facultad de Ciencias Básicas y Biomédicas, Universidad Simón Bolívar, 080002, Barranquilla, Atlántico, Colombia.
Clínica de La Costa, 080020, Barranquilla, Atlántico, Colombia.
Sci Rep. 2024 Aug 30;14(1):20236. doi: 10.1038/s41598-024-70913-6.
Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.
系统性红斑狼疮（SLE）是一种多因素疾病，其特征是遗传、免疫和病毒因素的融合，导致内外因素的复杂相互作用。已广泛认识到 Epstein-Barr 病毒（EBV）和人类内源性逆转录病毒（HERV-E）作为 SLE 发病机制中的触发和维持因素的作用。以前的研究已经独立评估了 EBV 和 HERV-E 在这种疾病中的作用。在这项工作中，这些病毒因素首次在 SLE 患者中进行联合研究。本研究旨在评估免疫调节基因的差异表达以及特定病毒病原体（EBV 和 HERV-E）的发生率，以及 SLE 患者和对照组患者 T 和 B 淋巴细胞表面标志物的详细特征。对 SLE 患者和对照组参与者进行了比较分析，评估了参与免疫反应的表型标志物和基因（TNF-α、IL-2、IL-6、IL-10、IFNG、TLR3）的表达，以及 HERV-E 和 EBV 病毒基因（LMP1 和 BZLF1）的表达。本研究发现 SLE 与 EBV 之间存在显著关联。在 SLE 患者中观察到 EBV LMP1 基因表达显著增加。此外，还观察到 HERV-E 的显著过表达，以及在 SLE 患者中 T 和 B 淋巴细胞表面标志物 CD27+的分布显著增加，与对照组相比。这项研究提供了 EBV 病毒在 SLE 淋巴细胞中作用的证据，强调了病毒和宿主基因表达如何通过改变 TNF-α、IFN-γ 和 IL-10 介导的免疫调节途径以及平行过表达 HERV-E gag 来影响疾病发病机制，以及 TLR3 的减少可能表明抗病毒反应受损，这可能促进病毒重新激活并导致疾病活动。
