Data_Sheet_1_Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus.pdf

Systemic lupus erythematosus induced by biologics mainly results from tumor necrosis factor-alpha remains unclear. The objectives of the study were to investigate the mechanisms of tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus. Peripheral blood mononuclear cells obtained from thirteen psoriasis patients were cultured and treated with the following: untreated control, Streptococcus pyogenes with or without different biologics. The supernatants were collected for cytokines assay. Analysis of cytokine expression revealed that IL-2 and IL-10 levels decreased only in the TNF-α inhibitor-treated groups but not in the groups treated with biologics involving IL-17, IL-12/IL-23 or IL-23 inhibitor mechanisms (p < 0.001, p < 0.05). The IFN-γ/IL-13 ratio increased significantly in patients with SLE inducing biologics to S. pyogenes induction only compared with non-SLE inducing biologics to S. pyogenes induction only (p = 0.001). IL-2 and IL-10 depletion and a shift to the Th-1 pathway in the innate response are the correlated mechanism for tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus.

生物制剂诱导的系统性红斑狼疮（SLE）主要由肿瘤坏死因子-α引起，其具体机制尚不明确。本研究旨在探究肿瘤坏死因子-α抑制剂诱导系统性红斑狼疮的发病机制。通过对十三位银屑病患者的周围血单个核细胞进行培养并处理，包括未处理对照组、链球菌溶血素O（Streptococcus pyogenes）及其与不同生物制剂的联合处理。收集的上清液用于细胞因子检测。细胞因子表达分析显示，仅在接受肿瘤坏死因子-α抑制剂治疗的组别中，IL-2和IL-10水平降低，而在接受涉及IL-17、IL-12/IL-23或IL-23抑制剂机制的生物制剂治疗的组别中并未观察到这种现象（p < 0.001，p < 0.05）。与仅由链球菌溶血素O诱导的非SLE生物制剂诱导组相比，仅由链球菌溶血素O诱导的SLE生物制剂诱导组的IFN-γ/IL-13比值显著升高（p = 0.001）。IL-2和IL-10的耗竭以及向Th-1途径的转移，是肿瘤坏死因子-α抑制剂诱导系统性红斑狼疮的相关机制。