贝利尤单抗治疗儿童系统性红斑狼疮临床特点分析及对JAK/STAT信号通路相关分子表达的影响

Analysis of clinical characteristics and impact on the expression of molecules related to JAK/STAT signaling pathway in the treatment of systemic lupus erythematosus in children with belimumab

目的探究贝利尤单抗对儿童系统性红斑狼疮(SLE)疾病活动度、炎症因子水平、T/B/NK细胞亚群及JAK/STAT信号通路相关分子表达的影响。方法选取2021年4月至2022年4月广州市妇女儿童医疗中心收治的30例系统性红斑狼疮患儿,根据用药情况分为两组,10例使用贝利尤单抗治疗作为试验组,20例传统免疫抑制剂治疗作为疾病对照组。比较不同组别临床免疫指标、T/B/NK细胞亚群水平、炎症因子水平,JAK/STAT信号通路mRNA表达的蛋白水平。结果试验组用药3个月、用药6个月后CD4+T、CD19+B、干扰素(IFN)-ɑ、IFN-γ、肿瘤坏死因子(TNF)-ɑ、及白细胞介素(IL)-2、IL-4、IL-6、JAK1、STAT1、STAT3、STAT5、SOCS1、SOCS3与疾病对照组比较差异具有统计学意义(P<0.05)。试验组和疾病对照组STAT3、p-STAT3、SOCS3蛋白水平在治疗前与健康对照组比较差异有统计学意义(t=2.87,P=0.01),试验组治疗后STAT3、p-STAT3蛋白水平与健康对照组无显著性差异(t=1.81,P=0.07),疾病对照组治疗后STAT3、p-STAT3、SOCS3蛋白水平与健康对照组比较差异有统计学意义(t=2.75,P=0.01)。结论贝利尤单抗能有效的缓解低中度SLE的症状,显著改善机体的炎症状态和自身抗体水平,有效降低T/B/NK细胞亚群和炎症因子,具体作用机制可能与抑制JAK/STAT信号通路的活化和炎症因子的释放有关。

Objective To investigate the effects of belimumab on disease activity,inflammatory factor levels,T/B/NK cell subpopulations,and epression of JAK/STAT signaling pathway related molecules in children with systemic lupus erythematosus(SLE).Methods Totally 30 children with systemic lupus erythematosus admitted to Guangzhou Women and Children's Medical Center from April 2021 to April 2022 were selected,and another 10 healthy children who underwent normal physical examination were selected as the normal control group.The 30 children with SLE were divided into two groups based on medication:10 cases were treated with belizumab as the experimental group,and 20 cases were treated with immunosuppressive agents as the disease control group.Compare the clinical immune indicators,T/B/NK cell subgroup levels,inflammatory factor levels,and protein levels of JAK/STAT signaling pathway mRNA expression among three groups.Results After the experimental group received medication for 3 months and 6 months,there was statistical difference in CD4+,CD19+B,IFN-ɑ,IFN-γ,TNF-ɑ,IL-2,IL-6,JAK1,STAT1,STAT3,STAT5,SOCS1 and SOCS3 between the experimental group and the disease control group(P<0.05).There was a significant difference in protein levels of STAT3,p-STAT3,and SOCS3 between the experimental group and the disease control group before treatment and the normal control group(t=2.87,P=0.01).There was no significant difference in protein levels of STAT3 and p-STAT3 between the experimental group after treatment and the normal control group(t=1.81,P=0.07).There was still a significant difference in protein levels of STAT3,p-STAT3,and SOCS3 between the disease control group after treatment and the normal control group(t=2.75,P=0.01).Conclusion Belizumab can effectively alleviate the symptoms of low to moderate SLE,significantly improve the inflammatory state and autoantibody levels of the body,and effectively reduce T/B/NK cell subpopulations and inflammatory factors.The specific mechanism of action may be related to inhibiting the activation of JAK/STAT signaling pathway and the release of inflammatory factors.