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（biologics）诱发的系统性红斑狼疮（systemic lupus erythematosus, SLE），其与肿瘤坏死因子-α（tumor necrosis factor-alpha, TNF-α）相关的致病机制尚未明确。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具体机制。本研究从13名银屑病患者体内获取外周血单个核细胞（peripheral blood mononuclear cells, PBMCs），将其体外培养并分为以下组别：未处理对照组、化脓性链球菌（Streptococcus pyogenes）单独处理组，以及化脓性链球菌联合不同类别生物制剂处理组。收集各组细胞上清液用于细胞因子检测。细胞因子表达分析结果显示，仅在肿瘤坏死因子-α抑制剂处理组中，白细胞介素2（Interleukin-2, IL-2）与白细胞介素10（Interleukin-10, IL-10）的表达水平出现下调，而在靶向IL-17、IL-12/IL-23或IL-23的生物制剂处理组中未观察到此现象（p < 0.001, p < 0.05）。仅接受可诱发系统性红斑狼疮的生物制剂联合化脓性链球菌刺激的患者样本，其γ干扰素（Interferon-gamma, IFN-γ）/白细胞介素13（Interleukin-13, IL-13）比值较仅接受不可诱发系统性红斑狼疮的生物制剂联合化脓性链球菌刺激的组别显著升高（p = 0.001）。白细胞介素2与白细胞介素10的耗竭，以及固有免疫应答向Th1通路（T helper 1 pathway）的偏移，是肿瘤坏死因子-α抑制剂诱导系统性红斑狼疮的相关致病机制。