Taming lupus-a new understanding of pathogenesis is leading to clinical advances.
Taming lupus-a new understanding of pathogenesis is leading to clinical advances.
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系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是对核自身抗原失去耐受性，产生致病性自身抗体，并损害多器官系统。多年来，SLE患者主要采用经验性免疫抑制治疗，这与大量毒性相关，并不总能充分控制疾病。专门针对疾病发病机制或进展的靶向治疗的开发已经滞后，主要是因为疾病的复杂性和异质性，以及难以为临床试验设计统一的结局指标。可以改善SLE治疗的最新进展包括鉴定影响疾病发展风险的遗传变异，增强对先天性和适应性免疫激活和耐受性调节的理解，解剖免疫细胞激活和炎症途径，阐明组织损伤的机制和标志物。这些发现，加上临床试验设计的改进，形成了一个平台，可以启动新一代狼疮疗法的开发。
Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the loss of tolerance to nuclear self antigens, the production of pathogenic autoantibodies and damage to multiple organ systems. Over the years, patients with SLE have been managed largely with empiric immunosuppressive therapies, which are associated with substantial toxicities and do not always provide adequate control of the disease. The development of targeted therapies that specifically address disease pathogenesis or progression has lagged, largely because of the complex and heterogeneous nature of the disease, as well as difficulties in designing uniform outcome measures for clinical trials. Recent advances that could improve the treatment of SLE include the identification of genetic variations that influence the risk of developing the disease, an enhanced understanding of innate and adaptive immune activation and regulation of tolerance, dissection of immune cell activation and inflammatory pathways and elucidation of mechanisms and markers of tissue damage. These discoveries, together with improvements in clinical trial design, form a platform from which to launch the development of a new generation of lupus therapies.
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