Division of Rheumatology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA.
Nat Rev Rheumatol. 2013 Dec;9(12):705-20. doi: 10.1038/nrrheum.2013.136. Epub 2013 Sep 10.
With the approval by the FDA in 2011 of a biologic agent (namely belimumab) for the treatment of systemic lupus erythematosus (SLE), optimism abounds that additional biologic (and nonbiologic) agents will be similarly endorsed. Given the numerous immune-based abnormalities associated with SLE, the potential therapeutic targets for biologic agents and the candidate biologic approaches are also numerous. These approaches include: biologic agents that promote B-cell depletion, B-cell inactivation, or the generation of regulatory B cells; biologic agents that induce T-cell tolerance, block T-cell activation and differentiation, or alter T-cell trafficking; biologic agents that target the B-cell activating factor (BAFF) axis, type I interferons, IL-6 and its receptor, or TNF; and the adoptive transfer of ex vivo-generated regulatory T cells. Owing to the great heterogeneity inherent to SLE, no single approach should be expected to be effective in all patients. As our understanding of the pathogenic mechanisms of SLE continues to expand, additional therapeutic targets and approaches will undoubtedly be identified and should be fully exploited.
2011 年,美国食品药品监督管理局(FDA)批准了一种生物制剂(即贝利尤单抗)用于治疗系统性红斑狼疮(SLE),人们普遍乐观地认为,将会有更多的生物制剂(和非生物制剂)被批准用于治疗。鉴于 SLE 与许多免疫相关的异常有关,生物制剂的潜在治疗靶点和候选生物制剂方法也很多。这些方法包括:促进 B 细胞耗竭、B 细胞失活或产生调节性 B 细胞的生物制剂;诱导 T 细胞耐受、阻断 T 细胞激活和分化或改变 T 细胞归巢的生物制剂;靶向 B 细胞激活因子(BAFF)轴、I 型干扰素、IL-6 及其受体或 TNF 的生物制剂;以及体外生成的调节性 T 细胞的过继转移。由于 SLE 固有的高度异质性,不应期望单一方法对所有患者都有效。随着我们对 SLE 发病机制的理解不断深入,无疑会发现更多的治疗靶点和方法,并应充分利用这些靶点和方法。