Li Hanchao, Ju Bomiao, Luo Jing, Zhu Li, Zhang Jing, Hu Nan, Mo Lingfei, Wang Yanhua, Tian Juan, Li Qian, Du Xinru, Liu Xinyi, He Lan
Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.
Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.
Eur J Pharmacol. 2025 Jan 15;987:177204. doi: 10.1016/j.ejphar.2024.177204. Epub 2024 Dec 11.
The type I interferon (IFN-I) response is crucial in systemic lupus erythematosus (SLE). The mRNA level of interferon-stimulated genes (ISGs) is widely used for evaluating the activity of IFN in SLE. However, the character of ISGs in belimumab-treated SLE patients has not be reported. In this study, we enrolled 53 SLE patients undergoing belimumab treatment and assessed their clinical responses at 3, 6, and 12 months. The expression levels of 25 ISGs in Peripheral blood mononuclear cells (PBMCs) were quantified at baseline and at 3 months using quantitative real-time PCR. Using Least absolute shrinkage and selection operator (LASSO)-logistic regression, five genes (CXCL10, EPSTI1, HECR6, IFI27, IFIH1) were identified to predict belimumab efficacy. The IFN signature score, a multivariate logistic regression model based on the change rates of these genes, positively predicted the SLE responder index (SRI) at 12 months, with an area under curve of 0.940 in receiver operating characteristic and favorable outcomes in decision curve analysis. Patients with an IFN signature score ≥0 had higher SRI response rates, better clinical markers (including SLE disease activity index 2000 scores, anti-dsDNA, IgG levels, daily doses of prednisone, and higher complement C3 and C4 levels), and faster B cell decline than those with scores <0. In conclusion, after 3 months of belimumab treatment, the expression levels of IFN-I-inducible genes varied, and the IFN signature score reliably forecasted the SRI response at 6 and 12 months.
I型干扰素（IFN-I）反应在系统性红斑狼疮（SLE）中至关重要。干扰素刺激基因（ISGs）的mRNA水平被广泛用于评估SLE中IFN的活性。然而，贝利尤单抗治疗的SLE患者中ISGs的特征尚未见报道。在本研究中，我们纳入了53例接受贝利尤单抗治疗的SLE患者，并在3、6和12个月时评估了他们的临床反应。使用定量实时PCR在基线和3个月时对外周血单个核细胞（PBMCs）中25个ISGs的表达水平进行定量。使用最小绝对收缩和选择算子（LASSO）-逻辑回归，鉴定出五个基因（CXCL10、EPSTI1、HECR6、IFI27、IFIH1）来预测贝利尤单抗的疗效。IFN特征评分是基于这些基因变化率的多变量逻辑回归模型，它能正向预测12个月时的SLE反应者指数（SRI），在受试者工作特征曲线下面积为0.940，决策曲线分析显示结果良好。IFN特征评分≥0的患者比评分<0的患者具有更高的SRI反应率、更好的临床指标（包括SLE疾病活动指数2000评分、抗双链DNA、IgG水平、泼尼松每日剂量，以及更高的补体C3和C4水平），并且B细胞下降更快。总之，贝利尤单抗治疗3个月后，I型干扰素诱导基因的表达水平有所不同，IFN特征评分可靠地预测了6个月和12个月时的SRI反应。
