Yasuda Shinsuke
a Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine , Hokkaido University , Sapporo , Japan.
Mod Rheumatol. 2019 Jan;29(1):60-69. doi: 10.1080/14397595.2018.1493909.
Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease that preferentially affects women of child-bearing age. Most current treatments for SLE with the exception of belimumab are not target-specific. Nontargeted therapy such as corticosteroids, cyclophosphamide, and other immunosuppressive drugs results in unwanted adverse effects. Although progress in treatment, including supportive therapy, has dramatically improved the prognosis of patients with SLE, better treatment drugs and protocols with fewer adverse effects and higher efficacy for the most severe form of SLE are needed. Advancements in genomics, immunology, and pathophysiology in the field of systemic autoimmunity have provided physicians with increasing knowledge, but the most appropriate treatment for each patient with SLE remains to be established. Therefore, the search for novel treatment targets in patients with SLE is ongoing. This review focuses on recent findings in the genetics of lupus and the abnormalities in cellular interactions, cytokine profiles, and intracellular signaling in patients with SLE. Novel molecular targets for lupus, mostly introduced through clinical trials, are then discussed based on these findings.
系统性红斑狼疮(SLE)是一种高度异质性的自身免疫性疾病,主要影响育龄女性。除贝利尤单抗外,目前大多数治疗SLE的方法都不是靶向特异性的。非靶向治疗,如皮质类固醇、环磷酰胺和其他免疫抑制药物,会产生不良副作用。尽管包括支持性治疗在内的治疗进展显著改善了SLE患者的预后,但仍需要疗效更好、副作用更少的治疗药物和方案来治疗最严重形式的SLE。系统性自身免疫领域在基因组学、免疫学和病理生理学方面的进展为医生提供了越来越多的知识,但针对每个SLE患者的最合适治疗方法仍有待确定。因此,寻找SLE患者的新治疗靶点的工作仍在进行中。本综述重点关注狼疮遗传学的最新发现以及SLE患者细胞相互作用、细胞因子谱和细胞内信号传导的异常情况。然后根据这些发现讨论主要通过临床试验引入的狼疮新分子靶点。