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摘要: 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。Abstract: 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.
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Key words:
- systemic lupus erythematosus /
- pathogenesis /
- biological agents /
- targeted therapy
作者贡献：沈田负责撰写论文初稿、修订论文；吴小川负责审校论文。利益冲突：所有作者均声明不存在利益冲突 -
表 1 SLE靶向治疗代表药物及其靶点
分类 靶点 代表药物 靶向B淋巴细胞 CD20 Rituximab(利妥昔单抗) CD22 Epratuzumab(依帕珠单抗) BAFF Belimumab(贝利尤单抗) Blys和APRIL Telitacicept(泰它西普) 靶向T淋巴细胞共刺激分子 CD80 Abatacept(阿巴西普) CD40L Dapirolizumab Pegol(达比罗珠单抗聚乙二醇) 靶向浆母细胞/浆细胞 CD38 Daratumumab(达雷妥尤单抗) 靶向浆细胞样树突状细胞 BDCA2 Litifilimab 靶向细胞因子 IL-6 Sirukumab(西鲁库单抗) IL-12/23 Ustekinumab(乌司奴单抗) IL-17A Secukinumab(苏金单抗) IL-23 Guselkumab(古塞库单抗) 靶向细胞内信号通路 TNFR Etanercept(依那西普) TLR7/8 Enpatoran(恩帕托兰) Ⅰ型IFN受体 Anifrolumab(阿尼鲁单抗) JAK1/2 Baricitinib(巴瑞替尼) JAK1/2/3 Tofacitinib(托法替布) 靶向细胞代谢 mTOR Sirolimus(西罗莫司) 靶向蛋白酶体 20S proteasome Bortezomib(硼替佐米) 新型钙调磷酸酶抑制剂 Calcineurin Voclosporin(伏环孢素) SLE: 系统性红斑狼疮；BDCA2:血液树突状细胞抗原2；IL: 白细胞介素；TNFR: 肿瘤坏死因子受体；TLR: Toll样受体；IFN: 干扰素；mTOR: 哺乳动物雷帕霉素靶蛋白 
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