系统性红斑狼疮:从发病机制到新型靶向治疗

Systemic Lupus Erythematosus:from Pathogenesis to New Targeted Therapies

系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种累及多器官/系统的自身免疫性疾病,其病因复杂,涉及分子遗传、表观遗传、先天性免疫、获得性免疫、种族、激素和环境因素等多个方面。近年来,随着免疫细胞的精细分型、全基因组关联研究、单细胞测序、多组学分析、基因编辑等技术的推广应用,人们对SLE的发病机制有了越来越深入的认识,同时也推动了各种靶向免疫细胞、共刺激分子、细胞因子/信号转导通路的单克隆抗体或小分子药物以及嵌合抗原受体T细胞免疫治疗的开发及临床研究。贝利尤单抗、泰它西普、阿尼鲁单抗以及伏环孢素获批临床应用,为中重度SLE患者尤其是难治性SLE患者提供了更多选择。

Systemic lupus erythematosus(SLE)is an autoimmune disease that affects multiple organs or systems.The etiology of SLE is complex,involving molecular genetics,epigenetics,innate immunity,acquired immunity,race,hormone and environmental factors.Recent progress in fine immunophenotyping,GWAS,single cell sequencing and multiomics analysis has enabled a deeper understanding of the pathogenesis of SLE.Various monoclonal antibodies or small molecule drugs targeting immune cells,costimulatory molecules,cytokines or signal transduction pathways,and CART cell immunotherapy have been developed or even applied in clinical treatment.The approval of belizumab,telitacicept,anifrolumab and voclosporin for SLE has given clinicians,researchers and patients greater confidence and more treatment options for patients with moderate to severe SLE,especially those with refractory SLE.