Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics; Hunan Clinical Medical Research Center of Major Skin Diseases and Skin Health, Changsha 410011.
Department of Nursing, Second Xiangya Hospital, Central South University, Changsha 410011.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021 Nov 28;46(11):1267-1275. doi: 10.11817/j.issn.1672-7347.2021.200056.
Systemic lupus erythematosus (SLE) is a chronic and autoimmunity-mediated diffuse connective tissue disease. The mainstay of treatments for SLE mainly relies on corticosteroids and immunosuppressants, which have a series of unavoidable side effects. Therefore, it is of fundamental importance to search novel therapeutic targets for better treatment with favorable efficacy and minor side effects. Recent studies shed light on potential therapeutic targets for SLE, mainly covering the followings: B-cell/plasmocyte-related targets [B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD20, CD22, CD19/FcγRIIb, Bruton tyrosine kinase (Btk), and proteasome], T cell-related targets [calcineurin, mammalian target of rapamycin (mTOR), regulatory factor X1 (RFX1), and Rho kinase], macrophage-related targets (macrophage migration inhibitory factor), intracellular signaling molecules, cytokines (cereblon, histone deacetylase 6, Janus activated kinase/signal transducer and activator of transcription), co-stimulating factors (CD28/B7, CD40/CD154), IgE autoantibody, and gut microbiome. Among them, belimumab (a humanized monoclonal antibody against B-lymphocyte stimulator) and telitacicept (a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein) have been sequentially approved for the clinical treatment of SLE in China. A variety of new targeted-therapy drugs are in the Phase 2 or Phase 3 clinical trials,among which anifrolumab (a human monoclonal antibody against type I interferon receptor subunit 1) has completed a Phase 3 clinical trial with good responses achieved, although its incidence of herpes zoster is higher than that in the control group. The research progress in both molecular mechanisms and new drug development for different therapeutic targets have greatly promoted our better and in-depth understanding of the pathogenesis of SLE, and have also reflected the complexity and heterogeneity of the disease. Successful development and clinical application of more novel therapies would no doubt usher in a new era of individualized treatment for SLE in the future.
系统性红斑狼疮（SLE）是一种慢性、自身免疫介导的弥漫性结缔组织病。SLE 的主要治疗方法主要依赖于皮质类固醇和免疫抑制剂，这些药物具有一系列不可避免的副作用。因此，寻找新的治疗靶点对于更好地治疗具有良好疗效和较小副作用至关重要。最近的研究揭示了 SLE 的一些潜在治疗靶点，主要包括以下几个方面：B 细胞/浆细胞相关靶点[B 细胞激活因子（BAFF）、增殖诱导配体（APRIL）、CD20、CD22、CD19/FcγRIIb、布鲁顿酪氨酸激酶（Btk）和蛋白酶体]、T 细胞相关靶点[钙调神经磷酸酶、哺乳动物雷帕霉素靶蛋白（mTOR）、调节因子 X1（RFX1）和 Rho 激酶]、巨噬细胞相关靶点（巨噬细胞移动抑制因子）、细胞内信号分子、细胞因子（cereblon、组蛋白去乙酰化酶 6、Janus 激活激酶/信号转导和转录激活因子）、共刺激因子（CD28/B7、CD40/CD154）、IgE 自身抗体和肠道微生物组。其中，贝利尤单抗（一种针对 B 淋巴细胞刺激物的人源化单克隆抗体）和替利单抗（一种重组人 B 淋巴细胞刺激物受体-抗体融合蛋白）已相继在中国获得批准用于 SLE 的临床治疗。多种新型靶向治疗药物处于 2 期或 3 期临床试验阶段，其中阿尼鲁单抗（一种针对 I 型干扰素受体亚单位 1 的人源单克隆抗体）已完成 3 期临床试验，取得了良好的疗效，但其疱疹发病率高于对照组。不同治疗靶点的分子机制和新药研发的研究进展极大地促进了我们对 SLE 发病机制的更好和深入的理解，也反映了疾病的复杂性和异质性。更多新型治疗方法的成功开发和临床应用无疑将为未来 SLE 的个体化治疗带来一个新时代。
