Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine , Los Angeles, CA, USA.
Expert Opin Ther Targets. 2020 Dec;24(12):1283-1302. doi: 10.1080/14728222.2020.1832464. Epub 2020 Dec 1.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a heterogeneous clinical presentation whose etiologies are multifactorial. A myriad of genetic, hormonal, immunologic, and environmental factors contribute to its pathogenesis, and its diverse biological basis and phenotypic presentations make development of therapeutics difficult. In the past decade, tens of therapeutic targets with hundreds of individual candidate therapeutics have been investigated.
We used a PUBMED database search through April 2020 to review the relevant literature. This review discusses therapeutic targets in the adaptive and innate immune systems, specifically: B cell surface antigens, B cell survival factors, Bruton's tyrosine kinase, costimulators, IL-12/IL-23, the calcineurin pathway, the JAK/STAT pathway, and interferons.
Our ever-improving understanding of SLE pathophysiology in the past decade has allowed us to identify new therapeutic targets. Multiple new drugs are on the horizon that target different elements of the adaptive and innate immune systems. SLE research remains challenging due to the heterogenous clinical presentation of SLE, confounding from background immunosuppressives being taken by SLE patients, animal models that inadequately recapitulate human disease, and imperfect and complicated outcome measures. Despite these limitations, research is promising and ongoing. The search for new therapies that target specific elements of SLE pathophysiology are discussed as well as key findings, pitfalls, and questions surrounding these targets.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，临床表现异质性强，病因涉及多种因素。许多遗传、激素、免疫和环境因素共同导致其发病机制，其多样化的生物学基础和表型表现使得治疗药物的开发变得困难。在过去的十年中，已经研究了数十个治疗靶点和数百种候选治疗药物。
我们使用了 2020 年 4 月之前的 PUBMED 数据库检索来回顾相关文献。本综述讨论了适应性和固有免疫系统中的治疗靶点，特别是：B 细胞表面抗原、B 细胞存活因子、布鲁顿酪氨酸激酶、共刺激因子、IL-12/IL-23、钙调神经磷酸酶途径、JAK/STAT 途径和干扰素。
在过去十年中，我们对 SLE 病理生理学的理解不断提高，这使我们能够确定新的治疗靶点。多种新型药物即将问世，针对适应性和固有免疫系统的不同元素。由于 SLE 的临床表现异质性、SLE 患者服用的背景免疫抑制剂的干扰、不能充分重现人类疾病的动物模型以及不完善和复杂的结果测量，SLE 研究仍然具有挑战性。尽管存在这些限制，但研究仍有希望并在继续进行。本文讨论了针对 SLE 病理生理学特定元素的新疗法的研究，并介绍了这些靶点的关键发现、陷阱和问题。
