Targeting the programmed cell death-1 pathway in rheumatoid arthritis.
Targeting the programmed cell death-1 pathway in rheumatoid arthritis.
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DOI：
10.1016/j.autrev.2017.05.025
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发表时间：
2017-08
影响因子：
13.6
通讯作者：
Mor A
中科院分区：
文献类型：
--
作者：
Sandigursky S;Silverman GJ;Mor A
自从TNF-α抑制剂和其他生物制剂的引入，许多治疗类风湿关节炎患者的临床结局已显著改善。然而，仍有相当比例的患者对已成为护理标准的当前药物不耐受或反应不足。虽然这些药剂中的大多数被设计为影响疾病的炎症特征，但在临床中也存在替代地靶向淋巴细胞亚群的药剂（例如，利妥昔单抗）或干扰淋巴细胞共受体信号传导途径（例如，阿巴西普）。部分由于它们能够协调导致关节损伤和疾病进展的下游炎症反应，T和B淋巴细胞的致病性扩增被认为在类风湿性关节炎的发病机制中起关键作用。对免疫调节的新见解已经提出了针对淋巴细胞的药物靶向的新方法。在这篇综述中，我们讨论了深入了解人类遗传学和我们的理解接口与类风湿性关节炎的发病机制提供了一个强有力的理由利用共抑制受体程序性细胞死亡-1信号通路作为一种更好的方法治疗这种慢性的，往往是渐进的破坏性关节疾病。
Since the introduction of TNF-α inhibitors and other biologic agents, the clinical outcome for many treated rheumatoid arthritis patients has significantly improved. However, there are still a substantial proportion of patients that are intolerant, or have inadequate responses, with current agents that have become the standards of care. While the majority of these agents are designed to affect the inflammatory features of the disease, there are also agents in the clinic that instead target lymphocyte subsets (e.g., rituximab) or interfere with lymphocyte co-receptor signaling pathways (e.g., abatacept). Due in part to their ability to orchestrate downstream inflammatory responses that lead to joint damage and disease progression, pathogenic expansions of T and B lymphocytes are appreciated to play key roles in the pathogenesis of rheumatoid arthritis. New insights into immune regulation have suggested novel approaches for the pharmacotherapeutic targeting of lymphocytes. In this review, we discuss deepening insights into human genetics and our understanding of the interface with rheumatoid arthritis pathogenesis providing a strong rationale for exploiting the co-inhibitory receptor programmed cell death-1 signaling pathway as a better approach for the treatment of this chronic, often progressive destructive joint disease.
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DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
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作者：
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